An overview of potential cardioprotective benefits of xanthophylls in atherosclerosis:an evidence-based review

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.

Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism,inflammation reaction and bile acid metabolism in ApoE^(-/-)mice

Atherosclerosis(AS)is the main pathological basis of cardiovascular diseases.Hence,the prevention and treatment strategies of AS have attracted great research attention.As a potential probiotic,Pararabacteroides distasonis has a positive regulatory effect on lipid metabolism and bile acids(BAs)profile.Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS,whose antiatherosclerotic effect may be associated with the promotion of gut probiotics.However,it remains unclear whether and how oligomeric procyanidins and P.distasonis combined(PPC)treatment can effectively alleviate high-fat diet(HFD)-induced AS.In this study,PPC treatment was found to significantly decrease atherosclerotic lesion,as well as alleviate the lipid metabolism disorder,inflammation and oxidative stress injury in ApoE^(-/-)mice.Surprisingly,targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs,and increased fecal BAs excretion.Further,quantitative polymerase chain reaction(qPCR)analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating Srb1 expression;In addition,PPC intervention promoted BA synthesis from cholesterol in liver by upregulating Cyp7a1 expression via suppression of the farnesoid X receptor(FXR)pathway,thus exhibiting a significant serum cholesterol-lowering effect.In summary,PPC attenuated HFD-induced AS in ApoE^(-/-)mice,which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.

Identification of novel genes associated with atherosclerosis in Bama miniature pig

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.

Study on the Mechanism of Action of Glyasperin A in the Treatment of Atherosclerosis Based on Network Pharmacology and Molecular Docking

[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.

Mechanism of Polygoni Cuspidati Rhizoma in treating atherosclerosis based on network pharmacology and molecular docking

Background:The incidence and prevalence of atherosclerosis(AS)is increasing every year and has becoming a major health issue of global concern.Polygoni Cuspidati Rhizoma(PCR)is a Chinese herb that is widely used clinically for the treating of AS.However,its pertinent targets and probable mechanisms,still need to be completely explored.Methods:Active compounds and targets for PCR and AS targets were screened using public databases.A“drug-component-disease target”network map was created and analyzed after using the Venn online tool to identify common targets and Cytoscape software to screen drug-disease core targets.Critical targets pathway enrichment analyses are conducted using the Metascape database.Using AutoDock Vina and Pymol software,docking validation and visualization of active components and core targets were carried out.Results:PCR was obtained for ten compounds with 105 AS-related targets.Rhein,quercetin,beta-sitosterol,and luteolin may be drug candidates,and the genes for AKT1,TNF,IL-6,EGFR,TP53,IL-1,RELA,and VEGFA are potential therapeutic targets,according to network analysis.PCR might modulate the AGE/RAGE,PI3K/Akt,IL-17 and NF-ᴋB signaling pathways against the development of AS.Molecular docking indicated that quercetin has high affinity for AKT1 and TNF gene targets.Conclusion:This study provides rare information and scientific basis for further exploration of PC in the treatment of AS.

Effects of ginkgo flavone aglycone on atherosclerosis based on network pharmacology,molecular docking,and in vitro experiments

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.

The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

Aim:To study the relationship between NLRP3(nucleotide oligomerization domain[NOD]-,leucine-rich repeats[LRR]-,and pyrin domain-containing protein 3)inflammasome and its downstream inflammatory factors in obstructive sleep apnea(OSA)patients with carotid atherosclerosis(CAS)under cigarette exposure,further exploring the risk factors of CAS in OSA patients.Methods:A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected.According to the detection results,they were divided into the OSA group,the CAS group,and the OSA combined CAS group;additionally,29 healthy subjects who underwent a physical examination were also included.According to whether they were smoking,the groups were further divided into smoking and non-smoking groups.The age,body mass index(BMI),blood pressure,apnea-hypopnea index(AHI),lowest blood oxygen saturation(LSaO2),carotid intima-media thickness(CIMT),levels of blood sugar,blood low-density lipoprotein cholesterol(LDLc),and serum NLRP3,interleukin-1β(IL-1β),and interleukin-18(IL-18)of all subjects were recorded.Results:The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group.The levels of serum NLRP3,IL-1β,and IL-18 in the OSA group were higher than those in the normal control group(P<0.05);and those in the OSA combined CAS group were higher than the OSA group and CAS group(P<0.05),regardless of cigarette exposure.Considering cigarette exposure,serum NLRP3,IL-1β,and IL-18 levels were higher in the OSA,CAS,and OSA combined CAS smoking groups than those in the non-smoking group(P<0.05).Under cigarette exposure,AHI,LDLc,NLRP3,IL-1β,and IL-18 were significantly positively correlated(P<0.05),and LSaO2 was negatively correlated with CAS in OSA(P<0.05).AHI,LSaO2,LDLc,NLRP3,and IL-1βare the risk factors for OSA combined with CAS.Conclusion:LSaO2,AHI,LDLc,NLRP3,and IL-1βare the important risk factors for OSA combined with CAS under cigarette exposure,and their levels can be used to predict the occurrence of CAS in OSA.

Fastunnel导管在颅内动脉狭窄介入治疗中的价值

目的探讨新型输送型球囊扩张导管(Fastunnel导管)在颅内动脉粥样硬化性狭窄介入治疗中的临床应用价值。方法回顾性分析2022-06—2024-02郑州大学第一附属医院采用Fastunnel导管治疗的18例颅内动脉粥样硬化性狭窄患者的临床资料,所有患者均接受球囊扩张联合支架成形术,分析患者的临床资料、治疗情况、手术成功率及术后并发症发生情况。结果18例患者均成功接受介入手术治疗,手术成功率100%。术前血管狭窄率(78.94±5.3)%,病变血管长度(7.14±2.14)mm。手术时长21~58(43.56±9.05)min,治疗期间射线暴露时间10~28(21.3±3.56)min,辐射剂量1526~5281(3436.50±626.39)mGy。术后血管狭窄率(13.50±4.94)%。所有患者围手术期及术后均未出现并发症。结论Fastunnel导管治疗颅内动脉粥样硬化性狭窄具有较好的疗效和安全性,可简化手术步骤,提高手术效率,具有良好的临床应用价值。

Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype

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.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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.

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes

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.

Danggui Shaoyao powder improves hepatic lipid metabolism in atherosclerosis mice via PPARγ-LXRα-ABCA1 pathway regulation

Objective:To observe the effects of Danggui Shaoyao powder(DSP)on hepatic lipid metabolism and further explore its mechanism of action by peroxisome proliferator-activated receptor(PPARγ)-liver X receptor(LXRα)-adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)pathway regulation.Methods: Eight C57BL/6J male mice were selected as the control group,and 24 ApoE^(−/−)male mice were randomly divided into the atherosclerosis model(AS)group,atorvastatin calcium(AC)group,and DSP group(n=8 each group).To establish an AS model,ApoE^(−/−)mice were fed a high-fat diet for 16 weeks.Pathologic changes in the aortic vasculature and liver were identified using Oil Red O staining.Triglyceride(TG),cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were determined in the livers using a single-reagent GPO-PAP method.Fluorescence quantitative polymerase chain reaction and western blot were used to observe and evaluate the mRNA and protein expression of the PPARγ-LXRα-ABCA1 intermediates in the liver.Results: After 16 weeks of a high-fat diet,ApoE^(−/−)mice showed more Oil Red O staining in the aorta and liver compared to the CONT group.Compared to the AS group,the DSP and AC treatment reduced aortic plaque and hepatic lipid deposition to varying degrees.Furthermore,DSP significantly reduced the hepatic lipid area in ApoE^(−/−)mice(P<.001)and decreased the levels of TG,TC,and LDL-C in liver(P<.001,P=.027,P<.001,respectively).DSP also significantly increased the levels of PPARγ,LXRα,ABCA1,and ABCG1 mRNA expression,as well as the PPARγ,LXRα,ABCA1,and ABCG1 protein expression in liver.Conclusion: DSP improved hepatic lipid metabolism via PPARγ-LXRα-ABCA1 pathway modulation for AS treatment.

Diffuse arterial atherosclerosis presenting with acute ischemic gastritis: A case report

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.

胞外酸化经ASIC1/RIP1途径抑制TFEB介导的巨噬细胞脂噬

目的 探讨胞外酸化对巨噬细胞脂噬的影响及其作用机制。方法 采用RAW264.7巨噬细胞,以pH 6.5培养液与25 mg/L氧化低密度脂蛋白(ox-LDL)共孵育24 h构建胞外酸化诱导的泡沫细胞模型。分别以ASIC1特异性阻断剂PcTx-1和RIP1抑制剂Nec-1干预胞外酸化诱导的RAW264.7巨噬细胞24 h,油红O染色检测细胞内脂质蓄积;蛋白质印迹(Western blot)检测总ASIC1、膜ASIC1、p-RIP1 Ser166、p-TFEB Ser142、LC3和p62蛋白的表达;激光共聚焦显微镜观察脂滴(Bodipy示踪)与自噬标志物LC3II和LAMP1共定位;透射电镜观察细胞内脂滴和脂噬泡的数量变化;胆固醇荧光试剂盒检测ABCA1介导的胆固醇流出。结果 与pH 7.4组相比较,pH 6.5胞外酸化组胞内的脂质蓄积和细胞质膜上的ASIC1蛋白表达显著增加,p-RIP1Ser166、p-TFEB Ser142水平升高,LC3II蛋白减少和p62蛋白增加,脂滴与LC3II和LAMP1的共定位都分别减少,细胞内的脂滴数量显著增加,自噬体和脂噬泡的数量则明显减少,ABCA1介导的巨噬细胞内胆固醇流出显著减少。然而,胞外酸化对RAW264.7巨噬细胞的上述效应能被ASIC1特异性阻断剂PcTx-1和RIP1抑制剂Nec-1所取消。结论 胞外酸化经激活ASIC1/RIP1途径促进TFEB磷酸化抑制巨噬细胞脂噬,ASIC1可能是防治动脉粥样硬化等脂质蓄积疾病的新靶点。

Association between Fundus Atherosclerosis and Carotid Arterial Atherosclerosis

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.

Calpain-1 Mediated Mitochondria ROS/NLRP3 Inflammasome in Atherosclerosis

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 Ca2+ for activation, and calpain or 2, which requires millimolar Ca2+ 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.

To explore the mechanism of Naodesheng tablets in the treatment of atherosclerosis based on network pharmacology and bioinformatics

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).

Exploration on the mechanism of Radix Astragali-Caulis Spatholobi by Qi-invigorating and blood-activating combination for the treatment of atherosclerosis based on network pharmacology

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.

Mechanism of Cordyceps sinensis in atherosclerosis treatment based on network pharmacology and molecular docking analysis

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.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.