Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus

BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.

基于ApoA-Ⅰ/Akt1/β-catenin/TGF-β通路探讨化瘀祛痰方改善ApoE~(-/-)AS小鼠主动脉内皮细胞间质转化的作用机制

目的基于ApoA-Ⅰ/Akt1/β-catenin/TGF-β通路探讨化瘀祛痰方对ApoE~(-/-)AS小鼠主动脉EndMT的作用机制。方法24只ApoE~(-/-)小鼠随机分为模型组、化瘀祛痰方组、辛伐他汀组,每组8只;C57BL/6J小鼠8只作为空白常对照组。ApoE~(-/-)小鼠给予高脂饲料喂养制备AS模型,C57BL/6J小鼠给予普通饲料喂养。12周后,开始灌胃,空白对照组和模型组灌胃等容积生理盐水,化瘀祛痰方组灌胃化瘀祛痰方20 g/(kg·d),辛伐他汀组灌胃辛伐他汀混悬液2.275 mg/(kg·d),每日1次,给药4周。采用全自动生化分析仪检测血清血脂水平;苏木精-伊红染色法(HE)观察主动脉病理组织形态表现;免疫荧光法检测主动脉EndMT程度;实时荧光定量PCR(RT-qPCR)法检测主动脉转录因子E盒结合锌指蛋白1(ZEB1)、TWIST mRNA表达水平;蛋白免疫印迹法(Western Blot)检测肝脏ApoA-Ⅰ、主动脉α-平滑肌肌动蛋白(α-SMA)、血管内皮钙粘蛋白(VE-Cadherin)、ZEB1、TWIST、Akt1、p-Akt1、β-catenin、p-β-catenin、TGF-β1、Smad2及p-Smad2蛋白表达水平。结果与空白对照组相比,模型组小鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平显著升高,高密度脂蛋白胆固醇(HDL-C)水平显著下降(P<0.05);主动脉内壁不平整光滑,可见多量的泡沫细胞聚集,形成粥样斑块,斑块附着处血管内膜明显增厚且结构紊乱,管腔中可见脱落的斑块碎;主动脉α-SMA、VE-Cadherin双染色阳性细胞明显增多,α-SMA蛋白表达水平明显升高,VE-Cadherin蛋白表达水平明显降低(P<0.05);主动脉转录因子ZEB1、TWIST mRNA及蛋白表达水平明显升高(P<0.05);主动脉TGF-β1、p-Smad2蛋白表达水平明显升高(P<0.05),肝脏ApoA-Ⅰ、主动脉p-Akt1及p-β-catenin蛋白表达水平明显降低(P<0.05);化瘀祛痰方干预后,小鼠血清TC、TG、LDL-C水平显著下降,HDL-C水平显著升高(P<0.05);主动脉内壁欠光滑,可见少量内皮细胞脱落,管壁厚度明显减轻;主动脉α-SMA、VE-Cadherin双染色阳性细胞明显减少,α-SMA蛋白表达水平明显降低,VE-Cadherin蛋白表达水平明显升高(P<0.05);主动脉转录因子ZEB1、TWIST mRNA及蛋白表达水平明显降低(P<0.05);主动脉TGF-β1、p-Smad2蛋白表达水平明显降低(P<0.05),肝脏ApoA-Ⅰ、主动脉p-Akt1及p-β-catenin蛋白表达水平明显升高(P<0.05)。结论化瘀祛痰方能够显著改善ApoE~(-/-)AS小鼠EndMT,其作用机制可能与调控ApoA-Ⅰ/Akt1/β-catenin/TGF-β通路,调节EndMT相关转录因子,进而调节EndMT基因表达有关。

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.

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.

Network pharmacology-based approach to understand the effect and mechanism of Tangzhiqing against atherosclerosis

Background:Tangzhiqing formula(TZQ)has powerful pharmacological effects on diabetes and hyperlipidemia.However,according to current studies,the action and molecular mechanisms of TZQ for the treatment of atherosclerosis are not fully understood.Methods:In this study,we employed a network pharmacology approach that integrates target prediction,network construction,Gene Ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and molecular docking.This comprehensive methodology was used to predict the potential targets of TZQ in the treatment of atherosclerosis(AS)and to further elucidate the pharmacological mechanisms involved.Results:The targets predicted in this study are all highly involved in the TNF-αsignaling pathway,NOD-like eceptor signaling pathway,apoptotic pathway,etc.APP,NCOA1,ESR1,CCND1,EGRF,RELA,and FOS are the core targets of TZQ regulation and play a central role in its anti-AS effect.Conclusion:This study elucidates the mechanisms of TZQ in treating AS,providing a theoretical foundation for future research.

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.

基于NLRP3/Caspase-1/IL-1β信号通路探讨心脉康方对动脉粥样硬化小鼠血管内皮细胞焦亡的影响

【目的】观察心脉康方对动脉粥样硬化小鼠的治疗作用及机制。【方法】采用高脂饲料喂饲法构建动脉粥样硬化ApoE-/-小鼠模型。将造模成功的小鼠随机分为4组,即模型组、阿托伐他汀组及心脉康方低、高剂量组,每组8只。另设正常组(8只小鼠)。各组给予相应干预12周后,采用油红O染色法观察主动脉病理变化,酶联免疫吸附分析(ELISA)测定血清中白细胞介素1β(IL-1β)和白细胞介素18(IL-18)的含量,实时定量聚合酶链反应(qPCR)法检测主动脉组织中与细胞焦亡相关的核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白水解酶1(Caspase-1)及炎症因子IL-1β、IL-18的mRNA表达水平,Western Blot法检测主动脉组织中NLRP3、Caspase-1、IL-1β、IL-18的蛋白表达水平。【结果】与正常组比较,模型组小鼠主动脉内层厚度显著增加,出现大量脂质斑块和炎症细胞浸润,血清中IL-1β、IL-18含量升高(P <0.01),主动脉组织NLRP3、Caspase-1、IL-1β、IL-18的mRNA和蛋白表达量显著升高(P <0.01);心脉康方高剂量组和阿托伐他汀组小鼠主动脉组织中脂滴和易损斑块面积明显减少,血清中IL-1β、IL-18水平降低(P <0.01),主动脉组织NLRP3、Caspase-1、IL-1β、IL-18的mRNA和蛋白表达量显著降低(P <0.01)。【结论】心脉康方可能通过调节NLRP3/Caspase-1/IL-1β信号通路,有效减轻动脉粥样硬化模型小鼠的血管内皮细胞炎症反应和细胞焦亡,从而发挥防治动脉粥样硬化的作用。

Oxidative stress:New insights on the association of nonalcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.

Hepatic steatosis is associated with an increased risk of carotid atherosclerosis

AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.

Association between high cystatin C levels and carotid atherosclerosis

AIM To investigate the association between carotid atherosclerosis and cystatin C(CysC) and to determine the optimal CysC cut-off value.METHODS One hundred twenty-eight subjects were included in this study. Atherosclerosis was defined as a maximum carotid plaque thickness(MCPT) of greater than 2 mm. A receiver operating characteristic curve analysis was used to determine the diagnostic value of serum CysC for atherosclerosis. The subjects were divided into two groups according to the CysC cut-off value. We screenedfor diabetes, hypertension, dyslipidemia, smoking status, alcohol consumption, and exercise behavior. The association between atherosclerosis and CysC levels was assessed using multivariate analysis.RESULTS The subjects were then divided into two groups according to the CysC cut-off value(0.73 mg/L). The median age of the high CysC group was 72 years(85% males), whereas that of the low CysC group was 61 years(63% males). The CysC levels were significantly correlated with Cr and estimated glomerular filtration rate(eGFR) values. Bodymass index, visceral fat area, hypertension, diabetes mellitus, and MCPT were significantly higher in the high CysC group than in the low CysC group. Furthermore, the eG FR was significantly lower in the high CysC group. Regarding lifestyle habits, only the exercise level was lower in the high CysC group than in the low CysC group. Multivariate analysis, adjusted for age and sex, revealed that high CysC levels were significantly associated with an MCPT of ≥ 2 mm(odds ratio: 2.92; 95%CI: 1.13-7.99).CONCLUSION Higher CysC levels were associated with an MCPT of ≥ 2 mm. The CysC cut-off value of 0.73 mg/L appears to aid in the diagnosis of atherosclerosis.

Increased heart rate and atherosclerosis: Potential implications of ivabradine therapy

Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the importance of acquiring new therapeutic options in this field. A reduction in elevated resting heart rate (HR) has long been postulated as a therapeutic approach in the management of cardiovascular disease. An increased HR has been shown to be associated with increased progression of coronary atherosclerosis in animal models and patients. A high HR has also been associated with a greatly increased risk of plaque rupture in patients with coronary atherosclerosis. Endothelial function may be an important link between HR and atherosclerosis. An increased HR has been shown experimentally to cause endothelial dysfunction. Inflammation plays a significant role in the pathogenesis and progression of atherosclerosis. In the literature, there is data that shows an association between HR and circulating markers of vascular inflammation. In addition, HR reduction by pharmacological intervention with ivabradine (a selective HR-lowering agent that acts by inhibiting the pacemaker ionic current If in sinoatrial node cells) reduces the formation of atherosclerotic plaques in animal models of lipid-induced atherosclerosis. The aim of this editorial is to review the possible role of ivabradine on atherosclerosis.

Baicalin and geniposide inhibit the development of atherosclerosis by increasing Wntl and inhibiting dickkopf-related protein-1 expression

Background Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wntl and dickkopf-related protein-1 （DKK1）. Methods The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wntt and nuclear factor-r,B （NF-κB） were measured with RT-PCR and Westem Blot. Serum levels of interleukin-12 （IL-12） were quantified with ELISA. Results The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wntl and decreased DKKI expression and elevated the ratio of Wntl/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide monoor combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial ceils stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wntl and decreased DKK1 expression and elevated the ratio of Wntl/DKK1. Condusions Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wntl and inhibit- ing DKK1 expression.

Glycemic and blood pressure control in older patients with hypertension and diabetes： association with carotid atherosclerosis

Backgroud Numerous studies have confirmed the effectiveness of slowing the progression of atherosclerosis by blood pressure （Bp） control in patients with hypertension and several studies also showed the efficacy of intensive glycemic control in decreasing progression of carotid intima-media thickness （CIMT） in patients with type 1 and type 2 diabetes. However, few studies have compared the relative importance of glycemic w＇. Bp control in patients with diabetes and hypertension. We aimed to investigate the association between Bp and glycemic control and subclinical carotid atherosclerosis in older patients with hypertension and type 2 diabetes. Methods In a cross-sectional study, B-mode high-resolution ultrasonography of the carotid artery was performed in 670 subjects （508 males and 162 females） aged 60 years or over who had self-reported hypertension and diabetes but no history of coronary heart disease or stroke. Subjects were categorized by their systolic blood pressure： tight control, 〈 130 mmHg; usual control, 130-139 mmHg; or uncontrolled, 〉 140 mmHg, and by their hemoglobin Alc （HbAlc） level： tight control, 〈 6.5%; usual control, 6.5%-7.5%; or uncontrolled, 〉 7.5%, respectively. Results The mean CIMT was 8.20 ±0.11 mm, and carotid plaque was found in 52.5% （352/670） subjects. Overall, 62.1% of the subjects had subclinical carotid atherosclerosis, defined as having either carotid plaque or elevated CIMT （≥ 1.1 ram）. The mean CIMT was significantly different between Bp control categories （7.60 ± 0.09 mm, 7.90 ±0.08 mm, and 8.60 ± 0.12 mm, respectively, P = 0.03） but not between glycemic control categories （8.20± 0.10 mm, 8.1 ±0.08 mm, and 8.40 ± 0.14 ram, respectively, P = 0.13） using ANCOVA analysis. Multivariable logistic regression adjusting for potential confounding factors showed that usual or uncontrolled Bp control were associated with having carotid plaque （OR = 1.08 and OR=1.42, respectively）, or elevated CIMT [Odd ratio （OR） = 1.17, 95% confidence interval （CI） 1.04-2.24, and OR = 1.54, 95% CI 1.36-2.96, respectively compared to tight Bp control; but did not show glycemic control as independent predictor of either having carotid plaque or elevated CIMT. Conclusions In older patients with hypertension and diabetes, blood pressure control, but not glycemic control is associated with subclinical carotid atherosclerosis.

Association between Serum Alkaline Phosphatase and Carotid Atherosclerosis in a Chinese Population: A Community-based Cross-sectional Study

Objective This study aimed to investigate the relationship between alkaline phosphatase(ALP) and common carotid intima media thickness(IMT), carotid plaque, and extracranial carotid artery stenosis(ECAS). Methods A total of 3,237 participants aged ≥ 40 years were recruited from Jidong community in 2013-2014. Participants were divided into five quintile groups based on their serum ALP levels. Carotid atherosclerosis was assessed using ultrasound. Abnormal IMT, carotid plaque, and ECAS were defined as IMT > 0.9 mm, IMT > 1.5 mm, and ≥ 50% stenosis in at least one extracranial carotid artery, respectively. Results Common carotid IMT values and the prevalence of carotid plaque increased across serum ALP quintiles. Higher ALP quintiles were correlated with an increased risk of abnormal IMT [fourth quintile: odds ratio(OR) 1.78, 95% confidence interval(CI) 1.13-2.82, P = 0.0135;fifth quintile: OR = 1.82, 95% CI: 1.15-2.87, P = 0.0110] and ECAS compared to the lowest quintile(fifth quintile: OR = 1.47, 95% CI: 1.09-1.97, P = 0.0106). The association between ALP and prevalence of carotid plaque became insignificant after adjustment for confounders. Conclusion Serum ALP levels were independently associated with abnormal common carotid IMT and ECAS. These conclusions need to be further corroborated in future prospective cohort studies.

Efficacy of Solitaire AB stent-release angioplasty in acute middle cerebral artery atherosclerosis obliterative cerebral infarction

BACKGROUND In both national and international studies,the safety and effectiveness of treatment with the Solitaire stent in patients with ischemic stroke caused by acute large vessel occlusion were good,and the disability rate was significantly reduced.However,there are currently only a few reports on the differences in endovascular treatment for different etiological classifications,especially in the anterior cranial circulation,aorta atherosclerotic stenosis,and acute thrombosis.AIM To investigate the efficacy of Solitaire AB stent-release angioplasty in patients with acute middle cerebral artery atherosclerosis obliterative cerebral infarction.METHODS Twenty-five patients with acute middle cerebral atherosclerosis obliterative cerebral infarction were retrospectively enrolled in this study from January 2017 to December 2019.The Solitaire AB stent was used to improve anterior blood flow to maintain modified cerebral infarction thrombolysis[modified thrombolysis in cerebral infarction(mTICI)]at the 2b/3 level or above,the stent was then unfolded and released.RESULTS All 25 patients underwent successful surgery,with an average recanalization time of 23 min.One patient died of cerebral hemorrhage and cerebral herniation after the operation.The National Institutes of Health Stroke Scale(NIHSS)scores immediately after surgery(7.5±5.6),at 24 h(5.5±5.6)and at 1 wk(3.6±6.7)compared with the preoperative NIHSS score(15.9±4.4),were significantly different(P<0.01).One case of restenosis was observed 3 mo after surgery(the stenosis rate was 50%without clinical symptoms),the modified Rankin scale scores were 0 points in 14 cases(56%),1 point in 4 cases(16%),2 points in 2 cases(8%),3 points in 3 cases(12%),4 points in 1 case(4%),and 6 points in 1 case(4%).CONCLUSION In acute middle cerebral artery atherosclerosis obliterative cerebral infarction,when the Solitaire AB stent is unfolded and the forward blood flow is maintained at mTICI level 2b/3 or higher,stent release may be a safe and effective treatment method;however,long-term observation and a larger sample size are required to verify these findings.