Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunctio...Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.展开更多
Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's gen...Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of atherosclerosis.Methods:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate genes.Candidate gene function prediction was performed using the online prediction tool STRING 12.0.Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.Results:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and TAP2.nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight changes.In addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.Conclusions:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.展开更多
[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were...[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.展开更多
Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for...Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.展开更多
Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classica...Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.展开更多
BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatmen...BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.展开更多
Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2...Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.展开更多
Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for ...Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.展开更多
Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinf...Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).展开更多
The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atheroscl...The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.展开更多
Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We sear...Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.展开更多
Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional ce...Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community h...Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early age.Atherosclerosis may form both during intrauterine development and in childhood.Nutrition plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the mother.In the present review,we examined the development of atherosclerosis and the prerequisites in childhood.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as ins...BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with T2DM.METHODS Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were included.The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level.The CAC score was determined from thoracic CT images using the Agatston scoring method.Myosteatosis was diagnosed according to Martin’s criteria.Severe CAC(SCAC)was defined when the CAC score exceeded 300.Logistic regression and decision tree analyses were performed.RESULTS A total of 652 patients with T2DM were enrolled.Among them,167(25.6%)patients had SCAC.Logistic regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of SCAC.Myosteatosis was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of atherosclerosis.The decision tree analyses prioritized older age as the primary variable for SCAC.In older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was myosteatosis.CONCLUSION Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional risk factors.展开更多
The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the...The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.展开更多
基金supported by the National Key R&D Program of China(YFD2100103).
文摘Atherosclerosis,as the most prevalent form of cardiovascular disease,is characterized by oxidized lowdensity lipoprotein(ox-LDL)accumulation in the vascular wall,increased inflammation of the large arteries,dysfunction of the endothelial cells(ECs)and vascular smooth muscle cells(VSMCs),which may eventually lead to the formation of plaques.Xanthophylls,one of the main groups of carotenoids,have been proposed as preventive agents or adjunct therapies to prevent and slow the progression of atherosclerosis due to their cardioprotective properties.However,the underlying preventive mechanism of action of xanthophylls on the pathogenesis of atherosclerosis remains unclear,and clinical evidence of the effect of xanthophylls on atherosclerosis have not yet been summarized and critically reviewed.In this regard,we conducted a comprehensive literature search in four scientific databases(Pub Med,Google Scholar,Science Direct and Web of Science)and carefully analyzed the existing evidence to provide meaningful insights on the association between xanthophylls and atherosclerosis from various aspects.Based on the evidence from in vitro and in vivo studies,we explored several potential mechanisms,including antioxidant effect,anti-inflammatory effect,regulation of lipid metabolism,and modulation of ECs and VSMCs dysfunction,and we found that a clear picture of regulatory pathways of xanthophylls on atherosclerosis prevention and treatment is still lacking.In addition,epidemiological studies suggested the possible relationship among high dietary intake of xanthophylls,high plasma/serum xanthophylls and a reduced risk of atherosclerosis.Direct evidence from interventional studies investigating the effect of xanthophylls on atherosclerosis is very sparse,whilst indirect clinical evidence was only limited to astaxanthin and lutein.Therefore,well-designed long-term randomized controlled trials(RCTs)are highly recommended for future studies to investigate the effective dose of different xanthophylls on atherosclerosis prevention and their possible ancillary effect in conjunction with drug therapies on different stages of atherosclerosis.
基金supported by the Special Scientific Research Project of Army Laboratory Animals(No.SYDW[2020]01)National Natural Science Foundation of ChinaNo.32370568。
文摘Background:Atherosclerosis is a chronic cardiovascular disease of great concern.However,it is difficult to establish a direct connection between conventional small animal models and clinical practice.The pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of atherosclerosis.Methods:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate genes.Candidate gene function prediction was performed using the online prediction tool STRING 12.0.Immunohistochemistry and immunofluorescence were used to detect the expression of proteins encoded by candidate genes.Results:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and TAP2.nsSNPs cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight changes.In addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner layer.Conclusions:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.
基金Supported by Project of Science and Technology Department of Guizhou Province([2019]1401ZK[2021]-546)Guizhou Provincial Health Commission(gzwkj2021-464)。
文摘[Objectives] This study was conducted to investigate the mechanism of action of glyasperin A in the treatment of atherosclerosis using a network pharmacology approach. [Methods] Targets related to atherosclerosis were searched in GeneCards database. An active ingredient-disease-target network was constructed by Cytoscape 3.7.1. A target protein interaction network was constructed by String database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the DAVID database. [Results] Glyasperin A acted on 36 atherosclerosis-related targets, and the biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, barrier, and lipid oxidation, etc. The results showed that glyasperin A acted on 36 atherosclerosis-related targets. The biofunctional and pathway enrichment analyses showed that it was mainly involved in response to xenobiotic stimulus, drug transport across blood-brain barrier, lipid oxidation, positive regulation of protein localization to nucleus, and hepoxilin biosynthetic process, and it played an anti-fatigue role through signal pathways such as serotonergic synapse, efferocytosis, arachidonic acid metabolism, chemical carcinogenesis-receptor activation and platelet activation. [Conclusions] Glyasperin A has multi-target and multi-pathway effects in the treatment of atherosclerosis. This study provides reference for further research on glyasperin A in the treatment of atherosclerosis.
基金supported by the Science and Technology Foundation of Basic Research Program of Guizhou Province([2023]General 371,[2020]1Y381)the Administration of Traditional Chinese Medicine of Guizhou Province(QZYY-2018-130)+3 种基金the project of Key Laboratory of Basic Pharmacology of Ministry of Education,Zunyi Medicial University(No.qianjiaoheKYzi[2022]395)the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of the affiliated hospital of Guizhou Medical University(GYFYNSFC-2021-55,GYFYNSFC-2021-56)the Cultivation Plan of the NSFC(National Natural Science Foundation of China)of Guizhou Medical University(21NSFCP13)the Science and Technology Foundation of Health Commission of Guizhou Province(gzwkj 2022-221).
文摘Background:Ginkgo flavone aglycones(GA),a Ginkgo(Ginkgo biloba)extract,has been proven to have good biological activity in atherosclerosis(AS)treatment.Moreover,its active compounds and the corresponding mechanism for the treatment of AS remain unclear.Methods:To evaluate and identify the potential pharmacological mechanisms of GA in AS treatment,the program Cytoscape was used to generate network mappings of the GA-AS-potential target gene.GO and KEGG enrichment analyses were performed to further investigate the potential mechanism of AS and the pharmacological properties of GA.A molecular docking approach was utilized to determine the GA components that interact with Akt.In vitro experiments were carried out to identify the anti-atherosclerotic effects of GA by targeting Akt.Results:Network pharmacological research determined that the active components of GA(quercetin,kaempferol,and isorhamnetin)correlated with AS target genes such as AKT1,EGFR,SRC,ESR1,PTGS2,MMP9,KDR,GSK3B,APP,and MMP2,respectively.GO enrichment and KEGG analysis showed that PI3K-Akt signaling may play an important role in GA treatment.Molecular docking experiments indicated that quercetin,kaempferol,and isorhamnetin integrate into the binding pockets of the most potentially beneficial GA-AS target protein(Akt).Consequently,cell experiments were conducted to support the anti-atherosclerotic activity of GA on AS by inhibiting the phosphorylation of AKT1 and its downstream signaling molecules,which regulated the proliferation of HASMCs.Conclusion:Our results detailed GA's active ingredients,potential targets,and molecular basis against AS.GA may exert anti-atherosclerotic effects by suppressing Akt phosphorylation and inhibiting the proliferation of HASMCs.It also proposed a viable approach to determining the scientific foundation and therapeutic mechanism of Chinese herbal medicine extracts in disease therapy.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2020MH138(to XZ).
文摘Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)mice.However,little is known about the role of lnc_000048 in classically activated macrophage(M1)polarization.In this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages.Flow cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048.Flow cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite effect.Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization.Moreover,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR.Immunofluorescence(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage.We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression.Taken together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.
文摘BACKGROUND Ischemic gastritis is a clinically rare disease with high mortality that infrequently reported in the medical literature and under-recognized clinically and histopatho-logically.Early diagnosis and treatment can only be achieved through upper gastrointestinal endoscopy after symptoms appear.CASE SUMMARY A 68-year-old woman with a history of intracranial aneurysm developed dizziness,chest tightness and unconsciousness for 2 d.Computed tomography angiography showed diffuse coronary atherosclerosis,moderate to severe stenosis in the proximal end of the left anterior descending branch,multiple calcified plaques in the proximal end of the circumflex branch and right coronary artery,and mild to moderate stenosis.The patient also developed diffuse atherosclerosis in the splenic and mesenteric arteries,with mild lumen stenosis and athero-sclerosis in the abdominal aorta and its branches.Endoscopy showed submucosal congestion and damage of the entire gastric mucosa,of which the fundus and body of the stomach were most seriously affected.The mucosa was swollen,with a deep purple color,surface erosion and dark red oozing blood.Pathological examination showed bleeding and necrosis of the gastric mucosa,with residual contours of the gastric glands,consistent with ischemic gastritis.CONCLUSION Ischemic gastritis is a rare disease that may be difficult to diagnose as its symptoms may be similar to those of other gastrointestinal diseases.Diagnosis is usually based on endoscopic and pathological examinations,which show insufficient blood supply to the gastric mucosa leading to mucosal damage and necrosis.
文摘Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.
文摘Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.
基金supported by a grant from Key Project of Education Commission of Hubei Province(D20202802).
文摘Background:Naodesheng tablets(NDST)was widely used in clinical treatment as a drug for cardiovascular diseases,but the mechanism for treating atherosclerosis was unknown.On the basis of network pharmacology and bioinformatics,predict the relevant targets and signalling pathways for NDST in the treatment of atherosclerosis.Methods:First,the targets of NDST and the targets for treating atherosclerosis were looked for in different databases.Next,Venny 2.1.0 was used to find the genes that overlapped between NDST and targets for treating atherosclerosis.Subsequently,the herb-active ingredient-target-disease were obtained to explore the hub compound.Furthermore,the Metascape database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“active ingredient-intersection target-pathway”network by Cytoscape software to gain the hub genes and pathways.Finally,molecular docking was used to verify the affinity of hub ingredients and hub genes.Results:In the results,67 active ingredients and 322 targets of NDST were selected in ingredients-targets network.154 overlapping targets of NDST(322)and atherosclerosis(1330)were obtained.Then,the herb-active ingredient-target-disease showed that quercetin,apigenin and luteolin were the hub ingredients to treat atherosclerosis.Further,the hub genes(PTGS2,RXRA,CASP3)and pathways(lipid and atherosclerosis)were accessed in active ingredient-intersection target-pathway.Finally,the results indicated that quercetin,apigenin and luteolin were better binding the PTGS2,RXRA,CASP3,especially PTGS2 and luteolin in molecular docking.Conclusion:In conclusion,quercetin,apigenin and luteolin,as the main ingredients of NDST could play a important role in PTGS2,RXRA,and CASP3 for treating atherosclerosis via the lipid and atherosclerosis(TNF signaling pathway).
基金Guangxi Key Research and Development Plan Project(Gui Ke AB18221095)China National Region Undergraduate Innovation and Entrepreneurship Training Program Funded Project(No.202110599016)Guangxi Zhuang Autonomous Region Undergraduate Innovation and Entrepreneurship Training Program Funded Project(No.S202210599105).
文摘The objective of this study was to investigate the main active ingredients,potential targets,and possible mechanisms of action of the combination of Radix Astragali and Caulis Spatholobi for the treatment of atherosclerosis using network pharmacology.The study aimed to provide a reference basis for the development of new formulations and clinical use of Chinese medicine.The main components of Radix Astragali and Caulis Spatholobi were obtained from the TCMSP,BATMAN-TCM database,and literature reports.The targets corresponding to the main components were imported into the Uniprot database to standardize the names,and target information was supplemented with the Swiss Target Prediction database.Disease-related targets were obtained from DrugBank,OMIM,CTD,GeneCards,and DisGeNET online databases.Venn tools were used to obtain the potential targets of Radix Astragali and Caulis Spatholobi for the treatment of AS.The intersecting genes were imported into the STRING 11.5 database to construct protein-protein interaction network maps and analyze their interactions.Cytoscape 3.7.1 software was used to mine their core targets.GO function and KEGG signaling pathway enrichment analysis were performed using the DAVID v2023q1 database.The results were imported into the“Bioinformatics Cloud Platform”to generate enrichment bubble maps.Finally,the“component-target-pathway”diagram was constructed using Cytoscape 3.7.1 software.The study found that 78 major active ingredients and 527 potential targets were obtained from Radix Astragali and Caulis Spatholobi.The main active components of the two in combination for the treatment of AS are quercetin,stigmasterol,kaempferol,luteolin,formononetin,etc.The key targets involve CDKN1A,E2F1,CDK4,CDK2,CDK1,RB1,TP53,CDKN1B,IL6,JUN,etc.The main pathways involved the AGE-RAGE signaling pathway in diabetic complications,cancer pathway,etc.The biological processes involved include positive regulation of gene expression,negative regulation of apoptotic process,etc.The study initially verified the feasibility of the combination of Radix Astragali-Caulis Spatholobi by Qi-invigorating(promoting human metabolic activity)and blood-activating for the treatment of AS.It demonstrated that the combination of Chinese medicine has multi-level,multi-target,and multi-pathway mechanisms of action to treat the disease,providing a reference basis for the development and utilization of new drugs.
基金supported by the Educational Commission of Hubei Province of China(D20222802).
文摘Background:The present study intented to delve into the molecular mechanism of Cordyceps sinensis(C.sinensis)in treating atherosclerosis by combining network pharmacology and molecular docking analysis.Methods:We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PubChem,and PharmMapper to screen out the active chemical ingredients of C.sinensis and the corresponding targets.The String database was used for the matching normalization of results,and the software Cytoscape 3.7.2 was adopted to establish the C.sinensis-active components-targets of action-disease network.The databases of Online Mendelian Inheritance in Man database,GeneCards,Therapeutic Target Database,and DisGNET were searched to yield the major targets of atherosclerosis(AS),which were matched with the active component targets of C.sinensis to identify the potential therapeutic targets.The String database was utilized to set up the protein-protein interaction network,and Cytoscape software was applied for topological analysis,which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database.Finally,the core components of C.sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL.Results:In total,7 bioactive ingredients of C.sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained,231 of which were associated with AS.The core targets involved in AS treatment with C.sinensis included MAPK1,SRC,PIK3R1,AKT1,and HSP90AA1.The enrichment analysis unveiled the primary pathways involved in these processes,such as pathways in cancer and lipid and atherosclerosis.Moreover,through molecular docking,it was found that the active ingredients of C.sinensis presented with strong binding capacities with their corresponding targets,and the strongest binding capacity was observed between peroxyergosterol and SRC.Conclusions:The present study revealed at the molecular level that C.sinensis played its role in AS treatment through multiple drug active components,targets of action and pathways,which would point out the direction and provide theoretic basis for future research.
基金supported by the National Natural Science Foundation of China(No.81573957,No.81874461 and No.82070307).
文摘Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular paradigm.However,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were reported.Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets.On the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden.Stem cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects.Given the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging.In this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation.The future challenges and improvements were also discussed.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
基金funded by the Russian Science Foundation(Grant No.23-45-00031).
文摘Atherosclerosis is extremely widespread.Traditionally,it is considered a disease of older people,who most often experience problems with the heart and blood vessels.While much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early age.Atherosclerosis may form both during intrauterine development and in childhood.Nutrition plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the mother.In the present review,we examined the development of atherosclerosis and the prerequisites in childhood.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
基金Supported by Research Fund for Lin He’s Academician Workstation of New Medicine and Clinical Translation in Jining Medical University,No.JYHL2021FMS11and Jining Key Research and Development Projects,No.2022YXNS009.
文摘BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with T2DM.METHODS Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were included.The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level.The CAC score was determined from thoracic CT images using the Agatston scoring method.Myosteatosis was diagnosed according to Martin’s criteria.Severe CAC(SCAC)was defined when the CAC score exceeded 300.Logistic regression and decision tree analyses were performed.RESULTS A total of 652 patients with T2DM were enrolled.Among them,167(25.6%)patients had SCAC.Logistic regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of SCAC.Myosteatosis was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of atherosclerosis.The decision tree analyses prioritized older age as the primary variable for SCAC.In older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was myosteatosis.CONCLUSION Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional risk factors.
文摘The liver is in charge of distributing and regulating the movement of qi throughout the whole body,coordinating the transportation and transformation of the internal organs in the middle part of the body,promoting the biochemical circulation of qi,blood,and body fluids,and regulating emotions.Liver dysfunction can disrupt the transportation and transformation of qi,blood,and body fluids,causing phlegm turbidity,blood stasis,and other unwanted symptoms.Poor regulation of emotion further aggravates the accumulation of pathological substances,resulting in the obstruction of heart vessels,and ultimately coronary heart disease(CHD).Through regulating lipid metabolism,inflammatory reaction,vasoactive substances,platelet function,neuroendocrine,and other factors,liver controlling dispersing qi plays a comprehensive role in the prognosis of atherosclerosis,the primary cause of CHD.Therefore,it is recommended to treat CHD from the perspective of liver-controlling dispersion.