Abstract:Aim To investigate the effect of long-term high-fat diet (HFD) on the number of bone marrow-derived mesenchymal stem cell (BMSC) subsets in elderly mice and its mechanism. Methods Forty week old male C57BL/6 wild type (WT) mice were randomly divided into three groups:WT+normal diet (ND) group, WT+HFD group and WT+HFD+N-acetylcysteine (NAC) group. Forty week old male transgene (TG) mice (overexpressing superoxide dismutase and glutathione peroxidase) were randomly divided into two groups:TG+ND group and TG+HFD group. The intervention period of each group was three months. The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), non-high density lipoprotein (non-HDL) and TC/HDL in each group were determined by Alere Cholestech LDX blood lipid analyzer. The quantity changes of BMSC subsets in bone marrow and peripheral blood were analyzed by flow cytometry. Cell proliferation was detected by 5-bromo-2′-deoxyuridine labeling method. Annexin V-fluorescein isothiocyanate/propidium iodide double staining method was used to detect cell apoptosis.The level of reactive oxygen species (ROS) was detected by flow cytometric ROS detection reagent labeling method. Results The production of ROS in BMSC of HFD mice increased significantly. NAC could reverse the levels of serum TC, TG, LDL and non-LDL in HFD mice. The number of BMSC subsets Lin－c-Kit＋ cells in bone marrow of HFD mice decreased significantly, but the number of Lin－c-Kit＋ cells in blood did not decrease. The numbers of BMSC subsets Lin－Sca-1⁺ or Lin－CD133⁺ cells were similar in bone marrow and blood of HFD mice and normal diet mice. HFD significantly inhibited the proliferation and increased apoptosis of bone marrow Lin－c-Kit＋ cells in vivo. NAC treatment or transgenic mouse model effectively prevented the production of ROS in BMSC and the reduction of bone marrow Lin－c-Kit＋ cells induced by HFD. Conclusion HFD selectively decreases the number of bone marrow BMSC subsets Lin－c-Kit＋ cells by increasing the production of ROS in elderly mice.

Abstract:Aim To investigate the relationship between serum osteoprotegerin (OPG) and in-stent restenosis (ISR) in patients with coronary heart disease complicated with diabetes after percutaneous coronary intervention (PCI). Methods From 1 652 diabetes patients undergoing PCI and follow-up angiography at approximately one year, 135 patients were diagnosed with ISR, while 85 patients without ISR were randomly included as controls. Serum OPG levels and biochemical indexes were examined. General clinical data of the study subjects were collected. Multivariable Logistic regression was used to analyze the independent risk factors of ISR. Results Serum OPG levels were significantly higher in patients with ISR than those without ISR (P＜0.001). Patients with ISR had higher rates of smoking, higher values of serum creatinine, total cholesterol, low density lipoprotein cholesterol (LDLC) and high sensitivity C-reactive protein (hs-CRP), lower values of glomerular filtration rate (GFR), more involved vessels, more severe lesions in coronary arteries, less treatment of dual antiplatelet therapy, diabetes control drugs and statins, and smaller stent diameter as compared with patients without ISR (all P＜0.05). The patients were further divided based upon the tertile distribution of OPG. Multivariable Logistic regression analysis showed that OPG level was an independent determinant of ISR with an odds ratio of 5.349(95%CI:2.049～13.967, P＝0.001) and 2.711 (95%CI:1.095～6.710, P＝0.031) for tertile 3 and 2 compared with tertile 1 after correction of possible confounding factors. Conclusion Serum OPG level is associated with the presence of ISR, and it is an independent risk factor of ISR in diabetes patients.

Abstract:Vascular aging is the pathological basis of cardiovascular and cerebrovascular diseases such as coronary heart disease, stroke and hypertension, which affects the occurrence, development and prognosis of a variety of diseases. Early identification of vascular aging is of great significance for screening, prevention and treatment of related diseases, judgment of prognosis and reduction of disease burden. But now in clinic it is mostly based on the physical properties of the blood vessel walls (such as hardness, elastic) to evaluate the aging condition of blood vessel, which evaluation way is single and lack of specific biological markers, therefore, it is the future research direction to enrich clinical detection methods, deeply study the occurrence and development mechanism of vascular aging, and search for new diagnostic biomarkers.Therefore, this paper summarized the current situation and new progress of evaluation methods of vascular aging.

Abstract:Aging is one of the important risk factors of cardiovascular disease. With the rapid aging process in the world, the morbidity and mortality of patients with cardiovascular aging diseases have also increased significantly. Non-coding RNA provides a new molecular perspective for exploring cardiovascular aging diseases. Many studies have shown that non-coding RNA plays an important role in cardiovascular aging. The purpose of this review is to elucidate the role and progress of non-coding RNA in the regulation of cardiovascular aging, and to provide new therapeutic strategies for cardiovascular aging diseases.

Abstract:Aim To investigate the new potential mechanisms of carotid atherosclerosis pathogenesis and explore the potential targets and pathways of berberine intervention in carotid atherosclerosis by bioinformatic research. Methods The study searched the Gene Expression Omnibus database of the National Center for Biotechnology Information (NCBI)and obtained the GSE28829 datasets of carotid atherosclerosis plaque gene expression microarray, screened the sample differentially expressed gene data for enrichment analysis. The potential targets of berberine were searched and obtained to be intersected with the differentially expressed genes of carotid atherosclerosis in order to obtain the potential targets of berberine intervention in carotid atherosclerosis. Enrichment analysis was performed and the core targets were screened. Results A total of 174 differentially expressed genes in carotid atherosclerosis were screened, involving chemokines, nuclear factor kappa B, Toll-like receptors, fatty acid degradation and other signaling pathways. Five potential targets of berberine in carotid atherosclerosis were screened, involving fluid shear and atherosclerosis, interleukin-17, tumor necrosis factor and other signaling pathways. Monocyte chemoattractant protein-1(MCP-1/CCL2), heme oxygenase 1(HO-1/HMOX1) and matrix metalloproteinase-9(MMP-9) were identified as the core targets of berberine intervening carotid atherosclerosis by topology and enrichment analysis. Conclusions Differentially expressed genes in carotid atherosclerosis are mainly enriched in signaling pathways such as inflammatory response and lipid metabolism; berberine may intervene in carotid atherosclerosis by mediating targets such as CCL2, HMOX1, MMP-9, and regulating fluid shear and atherosclerosis, interleukin-17, and tumor necrosis factor and other signaling pathways.

Abstract:Aim To investigate the effect of mulberry extract (ME) on inflammatory response and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS) and its molecular mechanism. Methods H9c2 cells in normal culture were cultured as control group; H9c2 cells were treated with 10 mg/L LPS as LPS group; H9c2 cells were treated with 0,0 and 200 mg/L ME, and then treated with 10 mg/L LPS, as low, medium and high concentration ME groups.After transfection of si-NC and si-S100B into H9c2 cells, the cells were treated with 10 mg/L LPS, as LPS＋si-NC group and LPS＋si-S100B group. After transfection of pcDNA and pcDNA-S100B into H9c2 cells, the cells were treated with 200 mg/L ME followed by 10 mg/L LPS, as LPS＋ME＋pcDNA group and LPS＋ME＋pcDNA-S100B group. The levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. Flow cytometry was used to detect apoptosis; Western blot was used to detect the expressions of Bcl-2, Bax and S100 calcium binding protein B (S100B); Real-time quantitative PCR was used to detect the expression of S100B mRNA. ResultsThe levels of TNF-α and IL-6 in cardiomyocytes treated with different concentrations of ME were significantly decreased, the apoptosis rate was significantly decreased, the expression of Bcl-2 was significantly increased, the expression of Bax was significantly decreased, and the expression of S100B was significantly decreased, with concentration-dependent manner (P＜0.05). Interference of S100B expression inhibited LPS-induced inflammatory response and apoptosis of cardiomyocytes. Overexpression of S100B reversed the inhibitory effect of ME on LPS-induced inflammatory response and apoptosis of cardiomyocytes. Conclusion ME can inhibit LPS-induced inflammatory response and apoptosis of cardiomyocytes, and its mechanism may be related to the down-regulation of S100B.

Abstract:Aim To explore the impact of coronavirus-2019 disease (COVID-19) pandemic on emergency reperfusion characteristics in patients with ST-segment elevation myocardial infarction (STEMI) from non-epicenter. Methods This was a retrospective study involved STEMI patients undergoing primary percutaneous coronary intervention(PPCI), who admitted to chest pain center in our hospital during the pandemic (from January 23 to March 29 in 2020) and the same period in 2019, excluding the patients with COVID-19. Clinical characteristics and reperfusion parameters were compared between the two groups. Results A total of 64 STEMI patients undergoing PPCI were enrolled in our study, including 13 patients during the pandemic and 51 patients during the same period in 2019. No differences occurred in admission signs, GRACE scores, arrival periods, transferred patterns,the period from door to troponin,and the period from first medical contact to dual antiplatelet between the two groups (P＞0.05). As compared with 2019, STEMI patients undergoing PPCI had an apparent reduction. Meanwhile, significant delays appeared in reperfusion parameters, including the period from symptom onset to first medical contact (10 h vs. 3.0 h, P＜0.001), the period from first medical contact to electrocardiogram (6 min vs. 3 min, P＜0.001), the period from door to troponin (15 min vs. 12 min, P＝0.048), the period from door to device (76 min vs. 62 min, P＝0.017), the period from telephone to catheter activated (15 min vs. 5 min, P＜0.001) and the period from catheter arrival to device (52 min vs. 41 min, P＝0.033). Conclusion Even in non-epicenter, the COVID-19 outbreak still delayed mechanical reperfusion significantly.

Abstract:Aim To identify the correlation between microRNA (miRNA) and low-response to clopidogrel in patients with coronary heart disease (CHD), and explore their diagnostic value as biomarkers of low-response to clopidogrel.Methods 158 patients with stable CHD were recruited as the research population. The maximum platelet aggregation rate (MPAR) induced by adenosine diphosphate (ADP) was measured using light transmission aggregometry for all these patients. Eventually, 35 patients of them whose MPAR≥65% were allocated to low-response group. For comparison, 35 age-and gender-matched patients with MPAR＜65% were allocated to normal-response group. The peripheral blood mononuclear cells (PBMC) were isolated from the blood samples of each patient to extract total RNA. The expression differences of miR-34a-5p, miR-370-3p, miR-432-5p and miR-495-3p in the two groups were detected by real-time quantitative PCR. The diagnostic value of differently expressed miRNA for low-response to clopidogrel were evaluated by correlation analysis and receiver-operating characteristic (ROC) curve analysis. Results Compared with normal-response group, the expressions of miR-34a-5p and miR-495-3p were significantly elevated in low-response group, and their fold changes were greater than 2 (P＜0.05). There was no significant difference in miR-370-3p and miR-432-5p expressions between two groups (P＞0.05). The expressions of miR-34a-5p and miR-495-3p were positively correlated with MPAR in CHD patients (r＝0.709, P＜0.01; r＝0.597, P＜0.01). ROC curve analysis showed that the area under the curve(AUC) of miR-34a-5p was 0.789, and the AUC of miR-495-3p was 0.787; while the AUC of miR-34a-5p+miR-495-3p was 0.873, which was significantly higher than that of miR-34a-5p (P＜0.05) or miR-495-3p (P＜0.05). Conclusion Both the high expression of miR-34a-5p and miR-495-3p were associated with low-response to clopidogrel in CHD patients, and may serve as novel biomarkers for low-response to clopidogrel in CHD.

Abstract:Aim To observe the effect of enhanced external counter pulsation (EECP) on endothelial dysfunction and the serum levels of endothelial cell specific molecule-1 (endocan-1) and fat specific serine protease (vaspin) in patients with coronary heart disease (CHD). Methods 200 patients with coronary heart disease who were treated in our hospital from November 2019 to June 2020 were selected as the research objects and randomly divided into control group (n＝98) and observation group (n＝102). The patients in the control group were given conventional drug treatment, and the patients in the observation group were added with EECP for 3 weeks. The therapeutic effect and the changes of vascular endothelial function indexes, serum endocan-1 and vaspin levels before and after treatment were compared between the two groups. Results The proportion of patients with angina relief, increased exercise tolerance, angina pectoris and exercise tolerance in the observation group were 82.35%, 75.49% and 65.69%, respectively, which were significantly higher than 45.92%, 35.71% and 24.49% in the control group (P＜0.05). After 3 weeks of treatment, the angina pectoris attack frequency, duration and total myocardial ischemia load in the observation group were significantly lower than those in the control group (P＜0.05). Flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) in the observation group were significantly increased after treatment, and the increase range in the observation group was significantly higher than those in the control group (P＜0.05). After treatment, serum endocan-1 in the observation group was significantly lower than that before treatment, while serum vaspin was significantly higher, and the changes of serum endocan-1 and vaspin in the observation group were significantly higher than those in the control group before and after treatment (P＜0.05). Conclusions EECP in the treatment of coronary heart disease has a significant effect, it can significantly improve the remission rate of coronary heart disease, improve vascular endothelial function and serum endocan-1, vaspin levels. The changes of serum endocan-1 and vaspin levels may be one of the mechanisms of EECP in protecting vascular endothelial function.

Abstract:Aim To explore the clinical effect of directional atherectomy in the treatment of superficial femoral arteriosclerosis obliterans. Methods A total of 42 patients with superficial femoral arteriosclerosis obliterans of the lower extremities were selected and randomly divided into observation group and control group, with 21 cases in each group. The observation group was treated with TurboHawk directional atherectomy system, and the control group was treated with balloon expansion and stent implantation. Collect data, observe and compare the treatment effects of the two groups. Results The postoperative clinical symptoms and ankle brachial index (ABI) improvement of the observation group were not significantly different from those of the control group (P＞0.05). The incidence of postoperative complications was lower in the observation group than that in the control group, and the difference was statistically significant (P＜0.05). Postoperative follow-up showed that the restenosis rate of the observation group was not significantly different from that of the control group (P＞0.05). Conclusions In the treatment of superficial femoral arteriosclerosis obliterans of lower extremities, directional atherectomy can achieve a patency rate similar to that of balloon dilatation and stent implantation. It is a safe, practical and effective method.

Abstract:Aim To evaluate the associations between single nucleotide polymorphisms (SNP) in lipoprotein(a) gene (LPA) and coronary heart disease (CHD). Methods PubMed, Embase, Web of Science, Cochran, CNKI and Wanfang database were searched to collect the studies focusing on the association of LPA gene rs10455872 and/or rs3798220 with CHD from the inception date of each database to June 0,1. Two researchers independently screened literatures, extracted information and assessed the risk of bias. Newcastle-Ottawa score (NOS) was used to evaluate the quality of each study. The heterogeneity among studies was assessed by I² and Cochran Q test. Random effect model was used to estimate odds ratio (OR) and 95% confidence interval (95%CI) when the heterogeneity was significant (I²≥50% and P＜0.05). The network Meta-analysis was applied to compare the effects of different SNP. Publication bias was analyzed using funnel plot and Egger’s test. RevMan 5.3 and R 4.0.5 were used for data analysis. P＜0.05 was considered as statistical significance. Results Of the 15 studies that were included in the analysis, 9 were analyzed for rs10455872 and 15 for rs3798220. The results of Meta-analysis demonstrated that the rs10455872_G and rs3798220_C alleles were significantly associated with CHD (rs10455872_G:OR 1.9,5%CI 1.10～1.30; rs3798220_C:OR 1.9,5%CI 1.27～2.00). In the dominant model, carriers of rs10455872_G allele had a 21% higher risk of CHD than participants with AA(OR 1.1,5% CI 1.11～1.32), and carriers of rs3798220_C allele had a 59% higher risk of CHD than participants with CC(OR 1.9,5%CI 1.26～2.02). Network Meta-analysis indicated that the carriers of rs3798220_C allele had higher risk of CHD. Conclusion LPA gene SNP were associated with CHD, individuals carrying the risk allele should pay more attention to prevent cardiovascular diseases.

Abstract:Studies have found that the ubiquitin-proteasome system plays an important role in both ubiquitination and deubiquitination, and involves in many cell biological processes. As an important part of the ubiquitin-proteasome system in eukaryotic cells, deubiquitinating enzyme can directly or indirectly affect inflammation, apoptosis,proliferation and other cellular activities,and regulate the process of atherosclerosis. In view of the importance of deubiquitinating enzyme, this article reviews the role and mechanism of deubiquitinating enzyme in atherosclerosis, providing evidence for clinical diagnosis and treatment of atherosclerosis.

Abstract:Myocardial remodeling after myocardial infarction is a complex pathological process, which seriously affects the prognosis of patients. CTRP9 is a newly discovered adipokine in recent years. A large number of studies have shown that CTRP9 can inhibit myocardial remodeling after myocardial infarction. This article reviews the related research of CTRP9 on myocardial remodeling after myocardial infarction.

Abstract:Clinical benefits of β-blockers in heart failure have been shown to vary in sinus rhythm and atrial fibrillation in recent years. However, there is no clear evidence on a large scale. This review mainly expounds the action mechanism of β-blockers for heart failure combined with atrial fibrillation and the main clinical research progress of different β-blockers for such diseases.

Abstract:Cardiovascular disease is the number one disease threatening human health. Myocardial infarction usually has an acute onset and high mortality, which brings a huge burden to patients and their families. How to reduce myocardial cell death is the main way to treat myocardial infarction. Although coronary intervention can reconstruct coronary blood flow after myocardial infarction, ischemia-reperfusion injury caused by revascularization will also damage cardiomyocytes and lead to cardiomyocyte death. Hippo signaling pathway has many functions, including promoting cell proliferation and regulating cell apoptosis. Therefore, whether Hippo signaling pathway can promote cardiomyocyte proliferation, reduce cardiomyocyte apoptosis and improve cardiac function in patients with myocardial infarction has become a research hotspot. This paper reviews the role and research progress of Hippo signaling pathway in myocardial infarction, so as to provide new ideas for clinical treatment of myocardial infarction.

Abstract:Dual antiplatelet therapy is the cornerstone of antithrombotic therapy in patients with acute coronary syndrome. Aspirin and P2Y12 receptor antagonists are commonly used antiplatelet drugs in clinic. At present, new P2Y12 receptor antagonists, especially ticagrelor monotherapy, are the subject of in-depth research in the field of antiplatelet optimization therapy. Studies have found that P2Y12 receptor antagonists can reduce thromboxane A2 receptor expression and thromboxane A2 production in platelets. Ticagrelor has broad-spectrum antiplatelet mechanism. This article summarizes the relevant research on the antiplatelet mechanism of new P2Y12 receptor antagonists, especially ticagrelor, and proposes new ideas for optimizing antiplatelet therapy.