Unveiling the oral-gut connection:chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE^(−/−)Mice on a high-fat diet

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE^(−/−)mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE^(−/−)mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

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.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

Background:To explore potential biomarkers for early diagnosis of atherosclerosis(AS)and provide basic data for further research on AS,the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.Methods:An AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet.Fasting serum samples were collected monthly for metabolomics and serum lipid detection.At the end of the treatment period,pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS,thereby distinguishing the susceptibility of mini-pigs to AS.The metabolomics was de-tected using a high-resolution untargeted metabolomic approach.Statistical analysis was used to identify metabolites associated with AS susceptibility.Results:Based on pathological analysis,mini-pigs were divided into two groups:a susceptible group(n=3)and a non-susceptible group(n=6).A total of 1318 metabo-lites were identified,with significant shifting of metabolic profiles over time in both groups.Dynamic monitoring analysis highlighted 57 metabolites that exhibited an ob-vious trend of differential changes between two groups with the advance of time.The KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis in-dicated significant disorders in cholesterol metabolism,primary bile acid metabolism,histidine metabolism,as well as taurine and hypotaurine metabolism.Conclusions:During the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet,the alterations in serum metabolic profile exhibited a time-dependent pattern,accompanied by notable disturbances in lipid metabolism,cholesterol me-tabolism,and amino acid metabolism.These metabolites may become potential bio-markers for early diagnosis of AS.

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study

BACKGROUND Previous studies have demonstrated the benefits of ideal cardiovascular health(CVH) in reducing cardiovascular risk.However,its role in subclinical atherosclerosis(SA) progression remains unclear.We aim to examine the association of CVH,estimated by the American Heart Association's new Life's Essential 8(LE8),with the progression of SA.METHODS This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for5.7 years.The LE8 score(range,0–100) consisted of blood pressure,lipids,glucose,body mass index,smoking status,diet health,physical activity and sleep health was evaluated in 1998 and 2008–2009.Progression of SA was determined by carotid plaque and coronary artery calcification(CAC) in 2008–2009 and 2013–2014.Log-binomial regression model was used to estimate the association of LE8 score with SA progression.RESULTS Each 10 points increment in LE8 score was associated with 15.2%(RR:0.848,95% CI:0.797–0.902),17.7%(RR:0.823,95% CI:0.766–0.884) and 12.0%(RR:0.880,95% CI:0.845–0.916) lower risks of carotid plaque,CAC and overall SA progression,respectively.Compared with participants with non-ideal CVH at both visits,the participants with ideal CVH at both visits had39.1%(RR:0.609,95% CI:0.494–0.752),41.0%(RR:0.590,95% CI:0.456–0.764) and 29.7%(RR:0.703,95% CI:0.598–0.825) lower risks of carotid plaque,CAC and overall SA progression,respectively.CONCLUSIONS Higher LE8 scores were associated with lower risks of SA progression.Besides,long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

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.

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

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.

Sonodynamic therapy for the treatment of atherosclerosis

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Atherosclerosis originating from childhood:Specific features

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.

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.

Silver carp muscle hydrolysate ameliorated atherosclerosis and liver injury in apoE^(-/-) mice: the modulator effects on enterohepatic cholesterol metabolism

Atherosclerosis(AS)is a major cause of cardiovascular diseases(CVDs)and a strong link with hepatic steatosis.Silver carp muscle hydrolysate(SCH)possess various beneficial activities but its effect on AS and hepatic steatosis is yet unknown.This study aimed to investigate the effects of SCH on AS lesions and hepatic steatosis using apoE-/-mice.Results showed that SCH significantly reduced the vascular AS plaques and alleviated hepatic steatosis lesions in apoE-/-mice.Consistent with this,the lipid levels both in circulation and liver were lowered by SCH.The mechanism analysis showed SCH down-regulated the expression of genes involved in lipoproteins production while up-regulated the expression of genes related to reverse cholesterol transport(RCT)in liver.Meanwhile,SCH remarkably promoted transintestinal cholesterol excretion(TICE)process in intestine,partly contributing to the reduction of blood lipids.The peptide profile data indicated LYF,HWPW,FPK,and YPR are the main peptides in SCH that play a vital role in alleviating AS lesions and hepatic steatosis.Our findings provided new knowledge for the application of SCH in ameliorating CVDs and liver diseases.

Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles

Rosuvastatin (RVS) is an excellent drug with anti-inflammatory and lipid-lowering properties in the academic and medical fields. However, this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia (HHcy), including high oral dosage, poor targeting, and long-term toxic side effects. In this study, we applied nanotechnology to construct a biomimetic nano-delivery system, macrophage membrane (Møm)-coated RVS-loaded Prussian blue (PB) nanoparticles (MPR NPs), for improving the bioavailability and targeting capacity of RVS, specifically to the plaque lesions associated with HHcy-induced atherosclerosis. In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4 (TLR4)/hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding and oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathways, reducing pyroptosis and inflammatory response in macrophages. Additionally, MPR NPs reversed the abnormal distribution of adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)/ATP binding cassette transporter G1 (ABCA1)/ATP binding cassette transporter G1 (ABCG1) caused by HIF-1α, promoting cholesterol efflux and reducing lipid deposition. In vivo studies using apolipoprotein E knockout (ApoE^(−/−)) mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable biosecurity, and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes. These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

Mesenchymal stem cell therapy in atherosclerosis:A bibliometric and visual analysis

BACKGROUND Mesenchymal stem cells(MSCs)are capable of self-renewal and differentiation,and extensive studies have demonstrated their therapeutic potential in atherosclerosis(AS).AIM To conduct a bibliometric analysis of studies on the use of MSC therapy for AS over the past two decades,assess key trends and provide insights for future research directions.METHODS We systematically searched the Web of Science Core Collection database for articles published between 1999 and 2023,yielding a total of 556 articles.Visual representation and bibliometric analysis of information and trends were facilitated using CiteSpace,the R package‘bibliometrix’and VOSviewer.RESULTS The analyzed articles were predominantly from 52 countries/regions,with prominent contributions from China and the United States.A cohort of 3057 authors contributed to these publications,with the works of Libby P distinguished by their influence and citation count.Int J Mol Sci has emerged as the journal with the highest publication volume,prominently disseminating influential papers and identifying citation outbreaks.Furthermore,our analysis identified current research hotspots within the field,focusing on vascular progenitor cells,inflammatory mechanisms,and extracellular vesicles.Emerging research frontiers,such as extracellular vesicles and oxidative stress,have been highlighted as areas of burgeoning interest.Finally,we offer perspectives on the status of research and future directions of MSC therapy in AS.CONCLUSION This comprehensive analysis provides valuable insights for advancing scientific research on MSC therapy for AS.By elucidating pivotal trends and research directions,this study aimed to foster innovation and promote the progress of disciplines in this field,thereby contributing to advancing scientific knowledge and clinical practice.

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.

E-cigarettes and arterial health:A review of the link between vaping and atherosclerosis progression

Recent studies have suggested an evolving understanding of the association be-tween vaping,specifically electronic cigarette(e-cigarette)use,and the progre-ssion of atherosclerosis,a significant contributor to cardiovascular disease.Des-pite the prevailing perception of vaping as a safer alternative to traditional toba-cco smoking,accumulating evidence suggests that the aerosols emitted by e-cigarettes contain harmful constituents that may promote endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia—key mechanisms implicated in atherosclerosis pathogenesis.While past research,including experimental studies and clinical investigations,has shed light on the potential cardiovascular risks associated with vaping,gaps in knowledge persist.Future research endeavors should focus on interpreting the long-term effects of vaping on atherosclerosis development and progression,exploring the impact of different e-cigarette formu-lations and user demographics,and identifying effective strategies for mitigating the cardiovascular consequences of vaping.By identifying and addressing these research gaps,we can enhance our understanding of the cardiovascular implica-tions of vaping and inform evidence-based interventions and policies to safe-guard public health.Core Tip:E-cigarette use has been linked to various cardiovascular risks,including the progression of atherosclerosis.Despite the perception of vaping as a safer alternative to smoking,evidence suggests that e-cigarette aerosols contain harmful substances that contribute to endothelial dysfunction,oxidative stress,inflammation,and dyslipidemia.These mechanisms are crucial in the development and progression of atherosclerosis.This review explores multiple facets of e-cigarettes and arterial health,focusing on the connection between vaping and atherosclerosis progression.It presents up-to-date evidence on pathophysiology and significant clinical implications,the impact of various constituents,and discusses contemporary public health strategies.

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.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

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.

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.

Shedding new light on atherosclerosis therapeutics:Nanomedicines targeting atherosclerotic immune microenvironment

Atherosclerosis(AS)leads to atherosclerotic cardiovascular disease(ASCVD),the predominant cause of death worldwide.As traditional lipid-lowering therapies have encountered a bottleneck in dealing with diverse types of atherosclerotic plaques and ASCVD,alternative therapies that can target other mechanisms are urgently needed.Recent studies have revealed that AS is rooted in disrupted immune responses,such as chronic local inflammation and autoimmune responses,and immunotherapies have emerged as a nascent avenue to control plaque development owing to their satisfactory effects and high cost efficiency.The atherosclerotic immune microenvironment(AIME)is the microenvironment in which diverse immune responses occur dynamically.AIME is characterized by persistent inflammatory responses,shifted immunometabolism,and the formation of adventitial neuroimmune cardiovascular interfaces,all of which are regarded as prospective targets for AS immunotherapy.Recently,the advent of nanotechnology has advanced AS immunotherapy targeting the AIME.Manifold nanoplatforms have greatly enriched AS therapeutics owing to their multimodal imaging and multichannel intervention capabilities.Here,we offer an overview of AIME and discuss how nanomedicines can assist in AS diagnosis and intervention.We introduce nanoplatforms integrated with imaging techniques,such as magnetic resonance imaging,photoacoustic imaging,fluorescence imaging,positron emission tomography,and ultrasound imaging,which can target AIME to realize plaque diagnosis.Moreover,we elaborated on nanomaterials that regulate innate immune responses,adaptive immune responses,and aberrant immunometabolism to achieve AIME modulation.Furthermore,we highlight the possible future directions of AS therapeutics,with a focus on AIME-targeted nanomedicines.