Abstract:Calcific aortic valve disease (CAVD) is characterized by thickening and calcification of the aortic valve, which can develop into valve sclerosis, and rapidly progress to a series of abnormal hemodynamic changes, and eventually heart failure and death. Aortic valve interstitial cells, as the main cell population of aortic valve, play a key role in the development of CAVD. The development of technologies such as single cell sequencing has improved researchers’ understanding of the origin, phenotype and functional heterogeneity of interstitial cells. This article reviews the role of interstitial cell heterogeneity in calcified aortic valve disease, which may provide a new idea for targeting interstitial cells to attentuate CAVD process.

Abstract:The vascular adventitia is layered with loose connective tissue, which includes external elastic lamina, vasa vasorum, and nerve ending. Fibroblasts are the main cellular components of the adventitia. In the previous studies, the vascular adventitia is considered to only play roles in nourishing blood vessels and maintaining the tension and structure of blood vessels. Recent studies have found that vascular adventitia secretes a variety of bioactive polypeptides as an autocrine/paracrine manner. These bioactive polypeptides play a vital role in the maintenance of vascular homeostasis and vascular injury diseases such as atherosclerosis, abdominal aortic aneurysm, hypertension, pulmonary arterial hypertension, vascular calcification and restenosis after angioplasty. Paying attention to and strengthening the research on the biological effects of paracrine/autocrine bioactive polypeptides from vascular adventitia and their roles in the maintenance of vascular homeostasis and injury diseases has important significance for the maintenance of vascular homeostasis and the understanding of the pathogenesis of vascular injury diseases.

Abstract:Annexin (ANX) is a highly conserved intracellular protein in the process of evolution. Its name originally comes from the Greek word “annexin”, meaning “to bind together”. ANX usually binds to the phospholipid of the cell membrane in a calcium-dependent manner and performs the functions of endocytosis, exocytosis, transport and signaling. Annexin A3 (ANXA3) is an important member of the ANX family, a large number of studies have found that there is an inseparable relationship between ANXA3 and the evolution of tumors. However, in recent years, with the deepening of the scientific research and development of bioinformatics technology, more and more studies have shown that ANXA3 may also play a huge role in the cardiovascular system, meanwhile, the underlying mechanism is still largely unknown. Therefore, the in-depth study of the specific role of ANXA3 in the physiology and pathophysiology of the cardiovascular system may provide new ideas and strategies for the prevention and treatment of cardiovascular diseases in the future.

Abstract:Aim To explore the characteristics of immune microenvironment of atherosclerosis based on the bioinformatics method of single cell transcriptome, and to explore the potential relationship between immune inflammation and atherosclerosis. Methods Single cell transcriptome data set GSE159677 was extracted from the GEO database to visually analyze the cellular components of carotid atherosclerotic plaque and its adjacent non-plaque area. CellChat was used to integrate intercellular communication networks, analyze the difference in intercellular interaction, identify the difference in the immune inflammatory signal pathway of atherosclerotic plaque, and explore the specific change pathway of intercellular receptor-ligand in the atherosclerotic immune microenvironment. Results In this study, the cellular composition, and cellular communication in atherosclerotic plaques were analyzed from the perspective of single cell sequencing. It was found that in the cellular composition of atherosclerotic plaques, endothelial cells and smooth muscle cells decreased, while T cells, monocytes, macrophages, and chondrocytes increased significantly. Through the analysis of cellular communication, it was found that there were significant changes in the communication between dendritic cells, monocytes, macrophages, natural killer cells, and endothelial cells, and between some cells and monocytes, including CXCL family and ACRK1, CCL family and ACRK1, MIF and CD74 and other ligand-receptor interactions. The communication of MIF, ANXA1, YNF, RETN, and LGASL9 to monocytes and the communication of NAMPT, CCL2, and TNFSF12 to endothelial cells play an important role in the immune inflammatory response regulating the development of atherosclerosis. Conclusion Immune inflammatory microenvironment plays an important role in the formation of atherosclerotic plaque.

Abstract:Aim To explore the mechanism of action of Sanleng-Ezhu herbal pair in the treatment of atherosclerosis (As) by using network pharmacology and molecular docking technology. Methods The relationship between related therapeutic targets was discovered and explored through TCMSP, Swiss Target Prediction, STRING database and Cytoscape software. GO enrichment analysis and KEGG pathway enrichment analysis were performed through the Omicshare platform. Molecular docking was performed by using the DockThor platform. Results 158 related therapeutic targets were found in the research results, including 49 core targets such as serine/threonine protein kinase 1, SRC proto-oncogene, tumor necrosis factor, mitogen-activated protein kinase 3, and interleukin-6. GO enrichment analysis found that the Sanleng-Ezhu herbal pair could affect the occurrence and development of As in many ways. KEGG pathway enrichment analysis found that the Sanleng-Ezhu herbal pair may play a role in the treatment of As through multiple metabolic pathways such as the C-type lectin receptor signaling pathway and the cancer pathway. Molecular docking showed that the binding activity of target TNF with hederagenin was the highest. Conclusion The mechanism of action of Sanleng-Ezhu herbal pair in the treatment of As is complex, and it mainly acts through multiple metabolic pathways such as C-type lectin receptor signaling pathway and cancer pathway.

Abstract:Aim To investigate the effect of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) on coronary heart disease (CHD) and its mechanism. Methods The expression levels of lncRNA HOTAIR, microRNA-126 (miR-126) and Polo-like kinase 4 (PLK4) in peripheral blood samples and endothelial progenitor cells (EPC) of CHD patients and healthy volunteers were detected by quantitative real-time PCR. EPC cell viability was detected by methyl thiazolyl tetrazolium assay. Apoptosis rate was detected by flow cytometry. The expressions of autophagy-related proteins LC3-Ⅱ and Beclin1 were detected by Western blot. Cell autophagy was observed by confocal microscopy. The relationship between lncRNA HOTAIR and miR-126 was analyzed by miRcode software and dual-luciferase reporter gene assay. The relationship between miR-126 and PLK4 was analyzed by TargetScan software and dual-luciferase reporter gene assay. The effect of lncRNA HOTAIR on mammalian target of rapamycin (mTOR) pathway through miR-126 in EPC was detected by Western blot. Results The expressions of lncRNA HOTAIR and PLK4 were significantly up-regulated in CHD blood samples and EPC (P＜0.01), and the expression of miR-126 was significantly down-regulated (P＜0.01). Down-regulation of lncRNA HOTAIR or PLK4 promoted autophagy in EPC, and inhibited CHD progression. Up-regulation of lncRNA HOTAIR inhibited EPC autophagy and promoted apoptosis through miR-126.The lncRNA HOTAIR activated the mTOR pathway in EPC via miR-126. Conclusion HOTAIR/miR-126/PLK4 axis mediates autophagy in EPC and affects CHD via mTOR signaling pathway.

Abstract:Aim To investigate the predictive value of remnant cholesterol in the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in coronary heart disease patients with high-normal blood pressure. Methods A total of 421 patients with high-normal blood pressure who underwent coronary angiography in the Department of Cardiology, General Hospital of Northern Theater Command from 2004 to 2014 were retrospectively analyzed. In this study, 97 patients with high-normal blood pressure who developed MACCE in this cohort were selected as the case group, and 97 patients with high-normal blood pressure who did not develop MACCE in the same cohort were selected as the control group by random number table for a case-control study. Results The number of patients with high-salt diet, the number of diabetic patients, the value of left ventricular end-diastolic diameter (LVEDD) and Gensini score in the case group were higher than those in the control group (which were 2.6,6.8,1.14 and 1.67 times of the control group respectively), the differences were statistically significant (P＜0.05). In lipid-related indicators, the levels of remnant cholesterol, triglyceride and total cholesterol in the case group were higher than those in the control group (which were 1.1,1.38 and 1.07 times of the control group respectively), the differences were statistically significant (P＜0.05). Logistic regression analysis showed that diabetes mellitus (OR＝14.4,5%CI:5.13～42.89, P＜0.01), high salt diet (OR＝6.6,5%CI:3.00～13.90, P＜0.01) and remnant cholesterol levels (OR＝10.7,5%CI:2.89～35.05, P＜0.01) were associated with MACCE in patients with high-normal blood pressure. The predictive value of remnant cholesterol for MACCE was evaluated by receiver operating characteristic (ROC) curve. The results showed that the area under ROC curve for remnant cholesterol to predict MACCE was 0.644 (95%CI:0.567～0.721). The optimal cut-off value was 0.52 mmol/L, and the sensitivity and specificity were 72.2% and 50.5%, respectively. Conclusion Diabetes mellitus, remnant cholesterol level and high-salt diet were independent risk factors for MACCE in patients with high-normal blood pressure, and remnant cholesterol level ＞0.52 mmol/L could predict the occurrence of MACCE in patients with high-normal blood pressure.

Abstract:Aim To explore the myocardial damage, abnormal electrocardiogram characteristics of patients infected with SARS-CoV-2 Omicron variant in Zhuhai. Methods 84 patients with SARS-CoV-2 Omicron variant (Omicron variant group) admitted to the Fifth Affiliated Hospital of Sun Yat-sen University from January 13 to March 0,2 were included, and 88 patients with non SARS-CoV-2 Omicron variant (non-Omicron variant group) from January 17 to February 7,0 were included. A retrospective study was conducted to compare myocardial damage, abnormal electrocardiogram and clinical characteristics between the two groups. Results The mean age of patients in Omicron variant group was smaller than that in non-Omicron variant group [(36.6±15.6) years vs. (49.8±14.3) years, P＜0.01], and the proportion of patients with body temperature, systolic blood pressure and fever at admission was lower than that of non-Omicron variant group (P＜0.05). The neutrophil/lymphocyte ratio [(2.93 (3.3,5.81) vs. 7.06 (2.2,1.27), P＜0.001], interleukin-2 (IL-2) and interleukin-6 (IL-6) levels in Omicron variant group were significantly lower than those in non-Omicron variant group (P＜0.01). Cardiac troponin I (cTnI) was negative in Omicron variant group, and the concentrations of cTnI, creatine kinase-MB isozyme (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and the proportion of patients with elevated levels were significantly lower than those of non-Omicron variant group (P＜0.01). The incidence of abnormal electrocardiogram in Omicron variant group was also significantly lower than that in non-Omicron variant group (25.0% vs. 42.0%, P＝0.001), sinus tachycardia, atrial premature beats and T wave changes were the main symptoms. Atrial premature beats,Tü wave changes, ST segment depression and bundle branch block were the main symptoms in non-Omicron variant group. Conclusions The patients infected with SARS-CoV-2 Omicron variant in Zhuhai may not have obvious myocardial damage because most of the patients have been vaccinated with COVID-19 vaccine. The incidence of abnormal electrocardiogram is also significantly lower than that of non-Omicron variant group, mainly sinus tachycardia, atrial premature beats and T wave changes.

Abstract:Aim To explore a novel experimental method for detecting cardiomyocyte proliferation at the live cell level, and to exclude false positive cells caused by multinucleate cardiomyocytes, so as to provide experimental reference for accurate detection of cardiomyocytes proliferation. Methods Use the cell division cyclin 20 (CDC20) and spastic paraplegia 20 (SPG20) as the molecular beacons targets. These molecular beacons allow for CDC20 and SPG20 detection in live cells, through Lipo-2000 transfection. The double positive cells are the proliferating ones that undergo cytokinesis. Results When the cells did not proliferate, the probes could not detect the target sequences and the cells cannot be detected by the fluorescence. When the nuclei replicated and divided without cytokinesis, the sequences could not be detected by both two probes at the same time, and the cells also could not be detected. When cells underwent mitosis with complete cytokinesis proliferation, both two fluorescence probes could be detected simultaneously. Conclusion The molecular beacons-based approach targeting CDC20 and SPG20 identified a proliferative subset of cardiomyocytes, which could exclude false positive problems of cell proliferation caused by nuclear proliferation and improve the accuracy of cell proliferation detection.

Abstract:With the change of daily life style and diet structure, the incidence of arterial stiffness is gradually increasing. The increase of atherosclerosis has become one of the important factors of cardiovascular events and all-cause mortality in the future. A healthy lifestyle, especially regular exercise and healthy diet, is a “first-line” strategy to prevent and/or treat vascular dysfunction with age. According to the influence of different exercise methods, exercise intensity and age on vascular function, this paper discusses the influence of exercise on vascular function, so as to provide reference for the prevention and/or treatment of arteriosclerosis and vascular function related diseases.

Abstract:Macrophages are a group of cells with diverse immune functions and high heterogeneity. Under the stimulation of different microenvironments, macrophages can be polarized into two subgroups:M1 and M2. There are significant differences in polarization phenotypes and function at different stages of myocardial fibrosis. That is, in the early stage of myocardial fibrosis, the proportion of M1 type increased to promote the progression of inflammation; in the later stage of myocardial fibrosis, the proportion of M2 type increased to alleviate myocardial fibrosis. The Notch signaling pathway can regulate macrophage polarization, which is related to the development of myocardial fibrosis, especially in cardiovascular diseases such as myocardial infarction and heart failure. Therefore, blocking the Notch signaling pathway is beneficial to regulating macrophage polarization, which is helpful to inhibit or reverse the process of myocardial fibrosis.

Abstract:Absent in melanoma 2 (AIM2) is a member of the PYHIN (pyrin and HIN domain-containing protein) family. It senses double-stranded DNA (dsDNA) and assembles the AIM2 inflammasome. Activation of AIM2 inflammasome causes cell pyroptosis as well as the release of interleukin (IL)-1β and IL-18, thereby leading to inflammation. The AIM2 inflammasome can become activated in atherosclerotic plaque and abdominal aortic aneurysm wall, and its activation has close links to the progression of atherosclerosis and abdominal aortic aneurysm. This review will focus on the structure and function of AIM2 and its role in atherosclerosis and abdominal aortic aneurysm.