Abstract:Atherosclerosis is a chronic vascular inflammation process. Emerging studies have shown that long non-coding RNA (lncRNA) can interact with microRNA as the competitive endogenous RNA (ceRNA), and regulate the expression and function of its target genes,which plays an important role in the pathogenesis of atherosclerosis. The novel regulatory mechanisms underlying the crosstalk among lncRNA, microRNA and mRNA are complex. This review comprehensively summarized the regulatory relationship of lncRNA-microRNA-mRNA axis in the pathophysiological processes of atherosclerosis, and highlighted the important role of this axis involved in endothelial cell dysfunction, vascular smooth muscle cell phenotype transformation, macrophage activation and lipid metabolism abnormality, aiming to provide new targets for clinical treatment of atherosclerotic diseases.

Abstract:Aim To investigate the role of microRNA-34a(miR-34a)in human aortic endothelial cells(HAEC)apoptosis during atherosclerosis(As)and the underlying mechanism. Methods HAEC were treated with oxidized low-density lipoprotein(ox-LDL). The expression level of miR-34a was detected using qRT-PCR. Apoptosis was determined via flow cytometry(FCM)and Caspase-3 activity assay. Prediction of the binding between miR-34a and 3′UTR of Sirt1 mRNA was performed by bioinformatics analysis and confirmed by a dual luciferase reporter assay. Results miR-34a expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAEC. Forced expression of miR-34a promoted HAEC apoptosis whereas inhibition of miR-34a could partly alleviate apoptotic cell death induced by ox-LDL. Further analysis identified Sirt1 as a direct target of miR-34a, and Sirt1 knockdown abolished the anti-apoptotic effect of miR-34a inhibitor. Moreover, overexpression of miR-34a enhanced the expression of acetylated of FoxO1, downregulation of miR-34a repressed the protein expression of acetylated-FoxO1. Conclusion Down-regulation of miR-34a inhibited HAEC apoptosis by regulating the expression of Sirt1/FoxO1 signaling pathway.

Abstract:Aim miR-155 can inhibit the formation of atherosclerotic plaques by interfering with the biological activity of vascular smooth muscle cells, but the specific mechanism is not very clear. The purpose of this study was to observe the effects of miR-155 on calcium sensing receptor(CaSR) expression in vascular smooth muscle cells, and to explore the role of CaSR in miR-155 in regulating the biological activity of vascular smooth muscle cells. Methods Vascular smooth muscle cells were cultured, and miR-155 mimic and Ad-CaSR were transfected into vascular smooth muscle cells. Western blot was used to detect the expression of related genes. MTT was used to determine the growth of vascular smooth muscle cells. Flow cytometry was used to detect the apoptosis of vascular smooth muscle cells. Transwell was used to detect the migration of vascular smooth muscle cell. Results The expression level of CaSR in miR-155 mimic group was significantly inhibited, the apoptosis of vascular smooth muscle cells was significantly reduced, and the proliferation and migration capabilities of vascular smooth muscle cells were significantly enhanced. Apoptosis of the cells was significantly increased, while the proliferation and migration capacity of vascular smooth muscle cells was significantly reduced. Conclusion miR-155 can regulate the growth of vascular smooth muscle cells, but this effect may be achieved by affecting the activity of CaSR in vascular smooth muscle cells.

Abstract:Aim To explore the expression and clinical significance of a novel long noncoding RNA n342721 (lncRNA n342721) in the serum of patients with acute myocardial infarction (AMI). Methods The expression of lncRNA in serum of 5 patients with AMI and 5 cases without coronary heart disease (non-CHD) was detected by using Human Transcriptome Array 2.0, and 6 up-regulated lncRNAs with different expression levels were screened out. Further verification and screening were carried out in serum of 20 patients with AMI and 20 cases with non-CHD and Jurkat T cells in vitro, and the most different lncRNA n342721 was selected for the study. In order to explore the clinical value of lncRNA n342721, the serum lncRNA n342721 expression and clinical data of 60 patients with AMI and 60 cases with non-CHD were analyzed. Furthermore, lncRNA n342721 was overexpressed and silenced at T cell level, then the changes of inflammatory cytokines such as interleukin-6 (IL-6), IL-10 and tumor necrosis factor α (TNF-α), and cholesterol transport related indexes such as liver X receptor β (LXR-β), ATP binding cassette transporter A1 (ABCA1) and ABCG1 were detected. Results Compared with non-CHD, 296 up-regulation and 74 down-regulation lncRNAs were detected among differentially expressed lncRNAs in the serum of AMI patients. Among the 6 selected lncRNAs, lncRNA n342721 was selected as the main research object, which had the greatest expression difference in serum and T cell levels. The results of quantitative real-time PCR showed that the expression of serum lncRNA n342721 in AMI group (n＝60) was significantly higher than that in non-CHD group (n＝60) (P＜0.05). Further logistic regression analysis showed that serum lncRNA n342721 was closely related to the occurrence of AMI. After construction of lncRNA n342721 overexpression lentivirus and transfection of T cells with small interfering RNA, it was found that, compared with the control group, the expressions of TNF-α and IL-6 increased in overexpression group (P＜0.05), the expressions of IL-10, LXR-β, ABCA1 and ABCG1 decreased (P＜0.05), the expressions of TNF-α and IL-6 decreased in silence group (P＜0.05), and the expressions of IL-10, LXR-β, ABCA1 and ABCG1 increased (P＜0.05). Conclusion As a new biomarker, serum lncRNA n342721 may promote the occurrence and development of AMI by promoting immune inflammatory response and inhibiting reverse cholesterol transport.

Abstract:Circular RNA (circRNA) is a new member of the non-coding RNA family, and because of its closed ring structure, it can be stably expressed in human blood. Lipid metabolism is one of the important biochemical reactions in human body, in which the processes closely related to atherosclerosis(As) are the endogenous pathway of lipid metabolism and reverse cholesterol transport(RCT). Abnormal lipid metabolism on the one hand is that excessive cholesterol accumulated in the cell can not be excreted to the liver for degradation, on the other hand, it will cause oxidative modification of low density lipoprotein(LDL) to oxidized low density lipoprotein(ox-LDL), which will also produce toxicity to cells while forming foam cells, and cause As. This paper summarizes that circRNA regulates RCT and the formation of ox-LDL to participate in the occurrence of As. At the same time, its stability is expected to become a new biomarker of As and provide a new research direction for the diagnosis and treatment of As.

Abstract:Aim To investigate the effect of overexpression of Bax inhibitor-1(BI-1) gene in cardiomyocytes on ischemia-reperfusion injury and its mechanism. Methods Thirty SD rats were randomly divided into sham operation group (sham group), ischemia-reperfusion group (I/R group), adenovirus control group (Ad-EGFP group), overexpression of BI-1 genome group (Ad-BI-1 group), cyclosporine A group (CsA group). After the establishment of myocardial ischemia-reperfusion injury(MIRI)model in rats, TTC staining was used to observe myocardial infarction area, TUNEL staining was used to observe myocardial apoptosis, ultrastructural changes of myocardial cells were observed under electron microscope; qRT-PCR was used to detect the expression of BI-1 mRNA in the myocardium of rats in each group. The myocardial cells of neonatal rats were isolated and cultured and divided into control group, hypoxia/reoxygenation group (H/R group), adenovirus control group (Ad-EGFP group), overexpression of BI-1 genome group (Ad-BI-1 group) and cyclosporine A group (CsA group) according to different cell treatment. The subcellular localization of BI-1 was detected by immunocytochemistry, the expression of BI-1 protein was detected by Western blot, and the MPTP opening level of myocardial mitochondria was detected by Calcein-AM; and the expression of apoptosis related proteins Bcl-2, Bax, CytC, Caspase-3 and Caspase-9 were detected by Western blot. Results Compared with sham group, myocardial infarct area, apoptosis number, mitochondrial structure damage in I/R group, Ad-EGFP group, Ad-BI-1 group and CSA group increased significantly (P＜0.05), while those in Ad-BI-1 group and CsA group decreased significantly (P＜0.05) compared with I/R group. qRT-PCR results showed that compared with sham group, BI-1 mRNA expression decreased significantly in I/R group, Ad-EGFP group and CsA group, while it increased significantly in Ad-BI-1 group; Subcellular location showed that BI-1 was mainly located in the endoplasmic reticulum of cardiomyocytes, and the fluorescence intensity of Calcein-AM was significantly lower in H/R group, Ad-EGFP group, Ad-BI-1 and CsA group than that in control group, while that of Ad-BI-1 and CsA group was significantly higher than that of H/R group; Compared with control group, the expression level of BI-1 protein was significantly decreased in H/R group, Ad-EGFP group and CsA group, but it was significantly increased in Ad-BI-1 group. Western blot results showed that compared with sham group, the ratio of Bcl-2/Bax decreased significantly in I/R group, Ad-EGFP group, Ad-BI-1 group and CsA group (P＜0.05), the expression of Caspase-3 and Caspase-9 increased significantly (P＜0.05); while the ratio of Bcl-2/Bax increased significantly in Ad-BI-1 group and CsA group compared with I/R group (P＜0.05), and the expression of Caspase-3 and Caspase-9 decreased significantly (P＜0.05). The expression of CytC was significantly higher in I/R group, Ad-EGFP group, Ad-BI-1 group and CsA group than that of sham group (P＜0.05). However, the expression of CytC in the mitochondria of myocardial cells was significantly lower in I/R group, Ad-EGFP group, Ad-BI-1 group and CsA group than that of sham group (P＜0.05), and the expression of CytC was significantly higher in the Ad-BI-1 group and the CsA group than that of I/R group (P＜0.05). Conclusion Overexpression of BI-1 gene can reduce the myocardial infarct area of MIRI rats, reduce the apoptosis of myocardial cells and improve the mitochondrial structure and function damage. The mechanism may be that overexpression of BI-1 can play the above role by changing the Bcl-2/Bax ratio, inhibiting the opening of MPTP, reducing the release of CytC, and reducing the activation of Caspase-3 and Caspase-9.

Abstract:Aim To study the effect of L-carnitine combined with CT10 regulator of kinase like protein (CrkL) on reducing myocardial cell injury induced by hypoxia/reoxygenation (H/R). Methods H9c2 cells were injured by H/R and treated with L-carnitine. CCK-8, flow cytometry, and Western blot were applied to determine cell proliferation, apoptosis, and nuclear associated antigen Ki67 (Ki-67), proliferating cell nuclear antigen (PCNA),Bü cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor-κB (NF-κB), and CrkL levels, respectively. Cells H9c2 were transfected with pcDNA-CrkL, and treated with H/R or treated with H/R and L-carritine. The above methods were used to detect cell proliferation and apoptosis.Results Compared with the control group, the viability , Ki-67, PCNA, Bcl-2, and CrkL protein expression of H9c2 cells were significantly decreased in the H/R group, and the apoptosis rate, Bax protein level, and the levels of inflammatory factors TNF-α, IL-1β, NF-κB were evidently increased (P＜0.05). Compared with the H/R group, L-carnitine obviously improved the H/R-induced H9c2 cell viability, Ki-67, PCNA, Bcl-2, and CrkL protein expression, and remarkably reduced the apoptosis rate, Bax protein level, and TNF-α, IL-1β, NF-κB levels (P＜0.05). CrkL overexpression dramatically enhanced H/R-induced H9c2 cell viability, Ki-67, PCNA, and Bcl-2 protein expression, while markedly reduced apoptosis rates, Bax protein levels, TNF-α, IL-1β, and NF-κB levels (P＜0.05). Compared with L-carnitine or CrkL overexpression alone, L-carnitine combined with CrkL overexpression clearly increased the viability of H9c2 cells, Ki-67, PCNA, and Bcl-2 protein expression, and distinctly reduced the apoptosis rate and Bax protein level, TNF-α, IL-1β, NF-κB levels (P＜0.05). Conclusion L-carnitine combined with CrkL promotes the proliferation of cardiomyocytes induced by H/R, reduces apoptosis and inflammatory response, and thus protects cardiomyocytes from damage.

Abstract:Aim To investigate the relationship between visceral adipose index (VAI) and lipid accumulation index(LAP) and carotid atherosclerosis (CAS) in high risk stroke patients. Methods The source of the case was 9 215 cases of high risk stroke population screened by 8 community hospitals in Fengtai District, Beijing. Collect complete demographic information and TCM syndrome scale through face-to-face questionnaire survey. Test items included physical examination, blood test and carotid ultrasound examination. The two indexes of VAI and LAP can be calculated by the formula. Statistical methods was used to explore the correlation between various indicators and carotid atherosclerosis, and stratified research was carried out. Results 9 215 subjects (mean age 60±9 years, 61.4% of women) were analyzed. The prevalence of carotid atherosclerosis was 74.7%. The levels of waist circumference, waist to height ratio (WHtR), female VAI, and female LAP was significantly higher in CAS group than those in control group (P＜0.001). Female visceral obesity replacement indexes were significantly correlated with carotid atherosclerosis (P＜0.001). Multivariate Logistic regression showed that age, gender (female), previous stroke history, hypertension, diabetes, smoking, and lack of physical exercise were independent risk factors for CAS in high risk stroke populations. Conclusion High high density lipoprotein cholesterol (HDLC) levels, eating vegetables, and fruits have a protective effect on carotid atherosclerosis. Female visceral obesity is significantly positively correlated with carotid atherosclerosis in stroke populations. The main risk factors affecting the formation of CAS are VAI, age, gender (female), history of previous stroke, hypertension, diabetes, smoking, lack of physical exercise.

Abstract:Aim To study the genotype distribution of PON1 rs662, ABCB1 rs1045642 in patients with acute minor stroke, and its effect on short-term prognosis. Methods Acute minor stroke patients were included who were admitted to the Department of Neurology, the First Affiliated Hospital of Xinjiang Medical University from September 2018 to June 2019. The genotypes of PON1 rs662 and ABCB1 rs1045642 were detected by digital fluorescence molecular hybridization, and the stroke recurrence were evaluated by follow-up after 3 months and 6 months respectively. The association between these gene polymorphism and stroke recurrence was also investigated. Results There was a difference in the distribution of ABCB1 rs1045642 genotypes among different races. There were more mutant homozygous types in Uygur population (42.8%). After 3 months follow-up, a total of 7 of the 150 patients had terminal events, including 5 patients with transient ischemic attack (TIA) and 2 patients with recurrent ischemic stroke. The risk of recurrence at 3 months after stroke with PON1 and ABCB1 homozygous mutations was not yet considered to be increased. After 6 months follow-up, a total of 21 of the 124 patients had endpoint events, including 14 patients with recurrent TIA and 7 patients with recurrent ischemic stroke. PON1 mutant type had a higher recurrence rate than the wild type and mutant heterozygous type after 6 months(OR=3.4,5%CI 1.384～10.404, P=0.016). Conclusion The distribution of each genotype of ABCB1 rs1045642 is different between Uyghur and Han, and there are more mutant homozygous (TT) genotypes in Uyghur population. PON1 mutation has a high recurrence rate of ischemic events, which is a risk factor for recurrence 6 months after acute minor stroke.

Abstract:Aim To investigate the relationship between plasma receptor interaction protein kinase 3 (RIPK3) and prognosis in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods A total of 287 ACS patients who were treated from November 2016 to November 2017 were selected as the study objects prospectively. Enzyme-linked immunosorbent assay was used to detect the level of RIPK3 in plasma and its relationship with prognosis was analyzed. Results The incidence of major adverse cardiovascular events (MACE) during follow-up of 287 patients with ACS was 23.00%. Plasma RIPK3 levels in patients with ACS with MACE were higher than those with non MACE, and the difference was statistically significant (P＜0.05). The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity of RIPK3 in predicting the prognosis of patients with ACS were 0.8,4.85%, and 95.02%, respectively. The incidence of poor prognosis in the high RIPK3 group was higher than in the low RIPK3 group, and the difference was statistically significant (P＜0.05). The median survival time of ACS patients in high-RIPK3 group was lower than that in low-RIPK3 group, and the difference was statistically significant (P＜0.05). COX regression analysis showed that chronic obstructive pulmonary disease, time from onset to consultation, total bilirubin, and RIPK3 were closely related to the prognosis of patients with ACS. Conclusion Plasma RIPK3 is closely related to the prognosis of patients with ACS. Detection of plasma RIPK3 level is helpful to understand the prognosis of patients.

Abstract:Aim To compare and evaluate the clinical effect of Y-type coronary artery bypass and sequential bypass in the near and medium term. Methods From January 2014 to December 5,0 patients were randomly selected as the study subjects. The patients with Y-pattern anastomosis of great saphenous vein were recorded as the experimental group and the patients with sequential anastomosis as the control group. The preoperative general condition, intraoperative blood flow at each anastomotic port of vein bridge, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), incidence of adverse cardiovascular events, CAG reexamination after admission due to similar symptoms were compared between the two groups. Results There was no significant difference in cardiac function between the two groups in the near future (3 months and 6 months after operation), and the incidence of adverse cardiovascular events was mainly in the middle postoperative period (2 and 3 years after operation) and later. There was no significant difference in body weight, age, cardiac function and instant blood flow measurement at each anastomotic site of venous bridge between the two groups before operation. Compared with the control group, the left ventricular ejection fraction (LVEF) of the observation group was significantly increased after 1,2 and 3 years of follow-up after operation(P＜0.05), while the incidence of adverse cardiovascular events, vascular bridge and anastomotic occlusion rate were significantly decreased (P＜0.05). Conclusion Compared with sequential coronary artery bypass grafting, Y-type saphenous vein bypass grafting can improve the postoperative cardiac function, reduce the incidence of postoperative complications and graft occlusion rate, which is of great significance to improve the mid-term survival rate of patients and worthy of clinical promotion.

Abstract:Premature coronary heart disease(pCHD)is a special type of cardiovascular disease. Recent research has demonstrated that pCHD possesses a strong genetic basis, genetic factors account for almost 50%~60% morbidity rate of pCHD, and lipid metabolism gene plays the most important role in it. Genetic variations of lipid metabolism can lead to the impediment of lipid synthesis and catabolism, as well as a series of disease characterized by atherosclerosis(As)and pCHD.This review aims to give a brief summary of the relationship between the genetic variations of lipid metabolism and pCHD.

Abstract:Atherosclerosis is the main factor leading to various cardio-cerebrovascular events, and it is also the main pathogenic mechanism of chronic diseases such as diabetes, hypertension and hyperlipidemia. Early diagnosis and early treatment are important measures to delay and control atherosclerosis. Pulse wave velocity, as an effective method to evaluate atherosclerosis, has been widely used in clinic because of its advantages of noninvasive, economical and simple operation. In this paper, the measurement principle and application of pulse wave velocity are reviewed.