Objective To investigate the potential causal associations between 731 immune cell traits and atherosclerosis by Mendelian randomization (MR) analysis. Methods Using single nucleotide polymorphisms (SNPs) as instrumental variables, genome-wide association study (GWAS) summary statistics (GCST90001391 to GCST90002121) for 731 immune cell traits were obtained from the GWAS Catalog database, and the atherosclerosis dataset (finn-b-I9_CORATHER) was retrieved from the IEU database for MR analysis. The inverse variance weighted method, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed to estimate the causal effects between the 731 immune cell traits and atherosclerosis, using odds ratio (OR) with 95% confidence interval (CI) as the effect size. Cochran Q test was used to assess heterogeneity. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method. Leave-one-out analysis was conducted to examine the sensitivity of the causal estimates to individual SNPs. Results MR analysis revealed potential causal associations between 24 immune cell traits and atherosclerosis (P<0.05). Among them, human leucocyte antigen (HLA)-DR on plasmacytoid dendritic cells (DC) [OR=1.035, 95%CI (1.016, 1.054), P<0.001] and hematopoietic stem cell absolute count (HSCAC) [OR=1.049, 95%CI (1.021, 1.077), P<0.001] showed significant positive causal associations with atherosclerosis (P≤0.001), whereas CD86 on CD62L+ myeloid DC [OR=0.953, 95%CI (0.926, 0.981), P=0.001] exhibited a significant negative causal association with atherosclerosis (P≤0.001). The results of Cochran Q test, MR-Egger regression, and MR-PRESSO indicated P-values>0.05, suggesting no evidence of heterogeneity or horizontal pleiotropy in the causal estimates for these three immune cell traits. Reverse MR analysis, using the 24 immune cell traits as outcome variables, showed no evidence of causal association (P>0.05), supporting a unidirectional causal relationship from immune cells to atherosclerosis. Conclusion HLA-DR on plasmacytoid DC and HSCAC may serve as risk factors for atherosclerosis, while CD86 on CD62L+ myeloid DC may play a protective role against atherosclerosis.
Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=−3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.
Atherosclerosis is a complex disease characterized by lipid accumulation in the vascular wall and influenced by multiple genetic and environmental factors. To understand the mechanisms of molecular regulation related to atherosclerosis better, a protein interaction network was constructed in the present study. Genes were collected in nucleotide database and interactions were downloaded from Biomolecular Object Network Database (BOND). The interactional data were imported into the software Cytoscape to construct the interaction network, and then the degree characteristics of the network were analyzed for Hub proteins. Statistical significance pathways and diseases were figured out by inputting Hub proteins to KOBAS2.0. The complete pathway network related to atherosclerosis was constructed. The results identified a series of key genes related to atherosclerosis, which would be the potential promising drug targets for effective prevention.
ObjectiveTo explore the association between hypertriglyceridemic waist (HTGW) and subclinical atherosclerosis among general Chinese population. MethodsPeople who took routine physical exam in the Sichuan Provincial People's Hospital were randomly selected from June 2011 to June 2012. We included those who received carotid artery ultrasonography and denied having symptoms of arterial ischemia, and screened the risk factors of cardiovascular disease (CVD) among them, including waist circumstance (WC) and triglycerides (TG). According to levels of WC and TG, the subjects were divided into three groups:Group I (those with normal levels of WC and TG); Group II (those with elevated levels of WC or TG); and Group Ⅲ (those with elevated WC and TG). ResultsA total of 484 subjects were included with average age of 47.3±11.3 years, of which, 72.1% of the subjects were male. The risk factors of CVD in Group I, Group II and Group III orderly increased, with significant differences. Then the subjects were stratified by age. For the elderly (no less than 60 years, n=75), the morbidities of subclinical atherosclerosis was 73.7% in Group I, 79.3% in Group II, and 70.4% in Group Ⅲ, respectively; and the results of univariate analysis and multivariate analysis showed that, HTGW was poorly associated with subclinical atherosclerosis in the elderly. For the young and middle-aged (less than 60 years, n=409), the morbidities were 19.8% in Group I, 35.1% in Group II, and 36.1% in Group III, respectively; after adjusting the confounding factors, Group II and Group III showed close association with subclinical atherosclerosis in the young and middle-aged when taking Group I as referent, with ORs (Group Ⅱ:1.987, 95%CI 1.073 to 3.679, P=0.029; and Group Ⅲ:2.060, 95%CI 1.020 to 4.161, P=0.044). ConclusionHTGW population has high-level risk factors of CVD which also present a tendency of aggregation. HTGW is closely associated with subclinical atherosclerosis in the young and middle-aged; while in the elderly, HTGW is poorly associated with subclinical atherosclerosis, but the morbidity of subclinical atherosclerosis is higher.
Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.
Sclerostin, as a bone-derived secreted glycoprotein, is a suppressor of Wnt signaling pathway. Recently, adverse cardiovascular events in the treatment of osteoporosis with sclerostin inhibitors have raised concerns about the association of sclerostin with atherosclerotic heart disease. Whether the role of sclerostin in atherosclerotic heart disease is harmful or beneficial is not clear. This article reviews the progress of the mechanisms of sclerostin in vascular calcification and atherosclerotic heart disease, focusing on the relationship between sclerostin and vascular calcification, the impact of its concentration changes on atherosclerotic heart disease, and the effect of sclerostin inhibitor on cardiovascular events.
摘要:目的: 探讨动脉硬化闭塞症(ASO)和静脉血栓形成(VT)患者同型半胱氨酸(Hcy)变化。 方法 :通过循环酶法对34例非动脉硬化闭塞症(ASO)和静脉血栓形成(VT)患者(对照组),30例动脉硬化闭塞症(ASO)患者和26例静脉血栓形成(VT)患者血液中Hcy进行测定。 结果 :循环酶法测定HCY的批内平均变异系数为2．23％,批间平均变异系数为1．59％。34例对照组,〖WTBX〗t =1135,〖WTBX〗P =0266gt;005;动脉硬化闭塞症(ASO)组Hcy含量明显高于对照组(〖WTBX〗P lt;O．05),静脉血栓形成(VT)组Hcy含量高于对照组(〖WTBX〗P lt;0．O5)。 结论 :高同型半胱氨酸血症可能是动脉硬化闭塞症(ASO)和静脉血栓形成(VT)及复发的致病因素。可将同型半胱氨酸作为动脉硬化闭塞症(ASO)和静脉血栓形成(VT)及复发的重要指标。Abstract: Objective: TO syudy the changes of the Homocysteine about Atherosclerosis obliterans and Venous thrombosis patients. Methods : To measure the Hcy in the blood of 34 healthy cases both non ASO and non VT(the comparison group),30 cases of ASO patients and 26 cases of VT patients respectively by enzymatic cycling assay。〖WTHZ〗Results :The average variation coefficient of Hcy within the groups was 223% and among the groups was 159% measured by enzymatic cycling assay.In the 34 cases of comparison group,t=1135,P=0266gt;005,The content of Hcy in the blood of ASO patients group were significantly higher than the comparision group (Plt;005),and the content of Hcy in the blood of VT patients group were also higher than the comparison group (Plt;005). Conclusion : Hyper Hcy may be the pathogenic diathesis to form or to recrudesce ASO and VT.So we can treat Hcy as the significant index to form or to recrudesce ASO and VT.
Atherosclerosis is a complex and multi-factorial pathophysiological process. Researches over the past decades have shown that the development of atherosclerotic vulnerable plaque is closely related to its components, morphology, and stress status. Biomechanical models have been developed by combining with medical imaging, biological experiments, and mechanical analysis, to study and analyze the biomechanical factors related to plaque vulnerability. Numerical simulation could quantify the dynamic changes of the microenvironment within the plaque, providing a method to represent the distribution of cellular and acellular components within the plaque microenvironment and to explore the interaction of lipid deposition, inflammation, angiogenesis, and other processes. Studying the pathological mechanism of plaque development would improve our understanding of cardiovascular disease and assist non-invasive inspection and early diagnosis of vulnerable plaques. The biomechanical models and numerical methods may serve as a theoretical support for designing and optimizing treatment strategies for vulnerable atherosclerosis.
ObjectiveTo explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages.MethodsThe expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, >60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. ResultsA total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01). Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting.ConclusionThe expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.