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.
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.
Coronary artery disease (CAD) is a cardiovascular disease mainly caused by atherosclerosis, which involves a variety of pathophysiological mechanisms such as lipid metabolism, inflammatory response, and endothelial dysfunction. Fetuin B is a glycoprotein secreted by the liver, which can participate in many processes such as cell inflammation, vascular calcification, and lipid metabolism, and is closely related to the pathogenesis of CAD. This article reviews the relationship between fetuin B and CAD and the mechanism of its occurrence and development, in order to provide new choices and methods for the prevention, diagnosis, and treatment of CAD.
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.
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.
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.
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.
Objective To investigate the management during offpump coronary artery bypass grafting (OPCAB) for patients with ascending aorta atherosclerosis and to find appropriate treatment for minimizing the postoperative cerebrovascular accidents. Methods 236 patients with ascending aorta atherosclerosis were retrospectively analyzed underwent OPCAB in this hospital from Sep.2004 to Dec.2007, 4 of them received “No-touch” technique, 35 of them had the proximal anastomoses with the Enclose assistant, and 197 of them had the proximal anastomoses with the assistant of Heartstring. Hemodynamic indexes were consecutively monitored, blood streams of grafts was monitored by transit time flow measurement (TTFM) to evaluate the quality. Results Distal anastomoses 881，proximal anastomoses 267, the blood stream of 881 grafts was monitored, the mean flow was 16.2±18.7 ml/min, and the pulsatility index (PI) were 4.9±2.3, indicating the good quality of all grafts. The change of hemodynamic indexes including mean artery pressure (MAP, 78.1±10.4 mmHg vs. 80.9±8.1 mmHg）, pulmonary capillary wedge pressure (PCWP, 11.9±3.6 vs. 10.9±2.1 mmHg）, mean pulmonary artery pressure (MPAP, 17.3±4.3 mmHg vs. 15.3±2.8 mmHg）, cardiac output (CO, 4.2±1.2 L/min vs. 4.5±1.6 L/min）, center vinous pressure (CVP, 9.2±2.3cmH2O vs. 9.3±1.8 cmH2O）, heart rate (HR, 71.4±14.0 beats/min vs. 73.4±16.5 beats/min）, there were no statistically difference between before and after proximal anastomoses (Pgt;0.05). Two patients died of low cardio output during operation, 4 patients with transient ischemic attack were improved by 2 months medical therapy, and others had no postoperative complications as perioperative myocardial infarction etc, and the time of stay hospital was 10.5±4.2d. Followup 3-24 months for 185 patients, all living patients had no myocardial or cerebrovascular accidents, the symptoms were alleviated and myocardiac function improved. Conclusion Assessing the degree of the ascending aorta atherosclerosis sufficiently before and during the operation, choosing different operational strategy, and decreasing the manipulation of aorta can decrease the incidence of cerebrovascular accident and get better clinical result.
Including gut microbiota and oral microbiota, various microorganisms in different human ecosystem constitute the human microbiota, which play an important role in human metabolism, immunity and maintaining microecological homeostasis. Abnormal changes in gut microbiota known as dysbiosis may lead to metabolic abnormalities and inflammatory changes, which are closely related to disease states including hypertension, diabetes, inflammatory bowel disease, and autoimmune diseases. The main cause of coronary artery disease is coronary atherosclerosis, a chronic and progressive inflammatory disease. Many evidences have shown that there is a correlation between gut microbiota and coronary artery disease. Therefore, we aim to review the relationship between gut microbiota and coronary artery disease, and discuss the possible research directions and application prospects.
Objective To investigate the predictive factors of clinical progression and short-term prognosis of cerebral infarction caused by large artery atherosclerosis (LAA). MethodsPatients with acute LAA cerebral infarction who were hospitalized in the Department of Neurology, Lianyungang Hospital of Traditional Chinese Medicine between January 2016 and May 2019 were included. On admission, the patients’ medical history was collected. The degree of neurological deficit was assessed, blood pressure, blood glucose, blood lipids, plasma homocysteine, lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured, and intracranial and extracranial blood vessels related test results were collected. Within 72 hours of onset, the Scandinavian Stroke Scale (SSS) was used to determine whether the patients’ condition progressed. The modified Rankin scale was used to evaluate the short-term prognosis at 30 days of onset. The related factors of clinical progression and short-term prognosis of LAA cerebral infarction were analyzed. Results Finally, 100 patients were included. According to the SSS assessment results within 72 hours of onset, 27 cases were divided into the progression group and 73 cases in the non-progression group. There was no significant difference in gender and age between the two groups (P>0.05). According to the evaluation results of the modified Rankin scale at 30 days of onset, they were divided into 31 cases in the poor prognosis group and 69 cases in the good prognosis group. There was no significant difference in gender and age between the two groups (P>0.05). Logistic regression analysis showed that plasma Lp-PLA2 [odds ratio (OR)=1.013, 95% confidence interval (CI) (1.007, 1.018), P<0.001], SSS score [OR=0.910, 95%CI (0.842, 0.985), P=0.019], and history of hypertension [OR=5.527, 95%CI (1.241, 24.613), P=0.025] were the predictors of disease progression within 72 hours. SSS score [OR=0.849, 95%CI (0.744, 0.930), P<0.001], carotid artery stenosis [OR=9.536, 95%CI (1.395, 65.169), P=0.021] and progressive stroke [OR=8.873, 95%CI (1.937, 40.640), P=0.005] were the predictors of short-term prognosis of LAA cerebral infarction. Conclusions History of hypertension and high levels of plasma Lp-PLA2 are predictors of early progression of cerebral infarction. Carotid artery stenosis and progressive stroke are predictors of adverse outcomes in the acute phase of cerebral infarction. Neurological scores on admission was a predictor for short-term adverse outcomes in the early and acute phases.