Abstract:Cardiac regeneration is an important approache for treatment of myocardial infarction and recovery of heart function. The key issue to cardiac regeneration is increasing the number of cardiomyocytes. Up-to-date, increasing studies have revealed that the cell resource of regenerated cardiomyocytes mainly involves three aspects:proliferated cardiomyocytes (cardiomyocytes reentering the cell cycle, activating mitosis procedure), direct reprogramming of somatic cell (cells transdifferentiated into cardiomyocytes directly), directional differentiation based on stem cells. Although stirring progress in the above 3 aspects has been gained, there are still many problems to be solved.

Abstract:Aim To investigate the effect of oxidized low density lipoprotein (ox-LDL) on activation of PPARγ-LXRα-ABCA1 pathway via lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) receptor. Methods The expression of liver X receptor α (LXRα) and ABCA1 was detected by stimulating J774A.1 macrophages with concentration gradient ox-LDL (0~40 mg/L, 12 h), the expression of LOX-1 was detected by laser confocal microscopy and Western blot, the transcriptional activation of peroxisome proliferators-activated receptor γ (PPARγ) was detected by double luciferase reporter gene, the expression of LXRα and ATP-binding cassette transporter A1 (ABCA1) protein was detected after incubation with J774A.1 macrophages by LOX-1 siRNA and PPARγ siRNA silencing, ox-LDL (30 mg/L,12 h). Results Ox-LDL significantly up-regulated the expression of LXRα and ABCA1 in J774A.1 cells (significantly different from the cell untreated by ox-LDL as control, P＜0.01, n＝3). LOX-1 overexpression of PPARγ double luciferase reporter gene system showed that ox-LDL increased the transcriptional activity of PPARγ by LOX-1. LOX-1 siRNA and PPARγ siRNA were treated with J774A.1 macrophages, respectively, and LXRα and ABCA1 were expressed (significantly different from the cell untreated by siRNA as control, P＜0.01, n＝3). Conclusion Ox-LDL activates PPARγ transcriptional activity by LOX-1 receptor, thereby upregulating LXRα and ABCA1 protein expression and activating PPARγ-LXRα-ABCA1 signal pathway.

Abstract:Aim To investigate the mechanism of glycogen synthase kinase 3β(GSK-3β)inhibitor lithium chloride on the proliferation of endothelial progenitor cells(EPC). Methods Mononuclear cells were isolated from bone marrow in rats by density gradient centrifugation combined. After 7 days, EPC were cultured with different concentrations of GSK-3β inhibitor lithium chloride. EPC proliferation were assessed by cells count and 3-{4,5-dimethylthiazol-2yl}-2,5-diphenyltetrazolium bromide (MTT) assay. The cell cycle of EPC was measured by fluorescence-activated cell sorting (FACS). The expression of phosphor-GSK-3β(pGSK-3β), β-catenin and cyclinD1 in EPC were detected by Western blot. Results Lithium chloride improved EPC proliferation. The number of EPC was obviously increased in lithium chloride group than that in control group. Compared with control group, EPC proliferation was enhanced in a dose-dependent manner in lithium chloride groups. S phrase in cell cycle was increased in lithium chloride group in comparison with control group by FACS assay. The protein expression of pGSK-3β, β-catenin and cyclinD1 were significantly higher than that in control group. Conclusion GSK-3β inhibitor lithium chloride could enhance EPC proliferation by activating Wnt signal pathway.

Abstract:Aim To investigate whether angiotensin(1-7) [Ang(1-7)]/Mas receptor axis protects human umbilical vein endothelial cells (HUVEC) against high glucose (HG)-induced injury by modulating ATP-sensitive K＋ channels (KATP channels). Methods Human umbilical vein endothelial cells were exposed to 40 mmol/L glucose to establish a model of HG-induced insults. The expression level of KATP channel protein was determined by Western blot, CCK-8 assay was used to test the cell viability, lactate dehydrogenase (LDH) activity in the culture medium was measured with commercial kits, Hoechst33258 staining was used to assess the number of apoptotic cells followed by photofluorography, the intracellular generation of reactive oxygen species (ROS) was measured by 2′, 7′-dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography, mitochondrial membrane potential (MMP) was detected by Rhodamine123 staining followed by photofluorography, the secretion levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Results Human umbilical vein endothelial cells were treated with 40 mmol/L glucose for 1～24 h, respectively. After human umbilical vein endothelial cells were exposed to HG for 3 h, the level of KATP channel protein decreased in a time-dependent manner, reaching the maximum decrease at the 24 h point. Co-treatment of the cells with 20 μmol/L Ang(1-7) and HG for 24 h ameliorated the down-regulation of KATP channel protein induced by HG.In addition, co-treatment of the cells with 20 μmol/L Ang(1-7) and HG or pre-treatment of the cells with 100 μmol/L pinacidil (a KATP channel opener) antagonized HG-induced injuries, evidenced by an increase in cell viability, a decrease in the activity of LDH, apoptotic cell number, ROS generation, MMP loss as well as the secretion levels of IL-1β and TNF-α. Co-treatment with 10 μmol/L A-779 (an inhibitor of Mas receptor) and HG or pre-treatment or 1 mmol/L glibenclamide (a KATP channel blocker) attenuated the above protective effects of Ang(1-7). Conclusion Ang(1-7)/Mas receptor axis protects human umbilical vein endothelial cells against HG-induced injury by modulating KATP channels.

Abstract:Aim To investigate the protection effect of microRNA-22 on ischemic cardiomyocyte. MethodsCardiomyocytes were transfected with microRNA-22 and cell activities were assessed. MTT was used to assess cell activities, EdU to assess DNA proliferation and Caspase-3 to assess cell apoptosis. Results MicroRNA-22 was transducted successfully using adeno-virus. The transduction efficiency reached 95%. Over-expression of microRNA-22 down-regulated PTEN level. Over-expression of microRNA-22 increased cell activities, DNA proliferation and decreased cell apoptosis. Conclusion Over-expression of microRNA-22 protected cardiomyocytes from ischemic injury.

Abstract:Aim To study the protective effect of trimetazidine (TMZ) on hypoxia jury in the rat cardiac myocytes. Methods Primary myocardial cells of rat were cultured in incubator at 37℃with 94%N₂₊₅%CO₂₊₁%O₂. Cell viability was detected by MTT. Apoptosis was detected by Hoechst staining. Mitochondrial membrane potential(MMP) was detected by TMRE. Mitochondrial energy metabolism was detected by Oxygraph-2k. Caspase-3, cytochrome C and respiratory chain complex enzymes were detected by Western blot. Results Hypoxia could induce apoptosis in the rat cardiac myocytes, decrease of MMP, cytochrome C release to cytosol. Furthermore, hypoxia could decrease state 3 respiration and respiratory control rate, increase state 4 respiration and decrease the expression of respiratory chain complex enzymes. Meanwhile, TMZ could play a protective effect against the apoptosis induced by hypoxia in the rat cardiac myocytes. It may be related to its protective role on MMP and respiratory chain complex enzymes. Conclusion TMZ could inhibit the apoptosis of rat cardiac myocytes induced by hypoxia via the mitochondrial pathway.

Abstract:Aim To investigate the role of galectin-3 (Gal-3) in ventricular remodeling of heart insufficiency, via the pathway of Gal-3 specific competitive antagonist--modified citrus pectin (MCP) inhibiting Gal-3. Methods 30 rabbits were randomly divided into sham operation group, cardiac insufficiency group and MCP group. A model of cardiac dysfunction after myocardial infarction was made by ligating the anterior descending branch of coronary artery. After the model was successfully made, MCP group was treated with 75 g/L MCP allocated with normal saline, and intragastric administration for 4 weeks with 2 mL/(kg·d), and sham operation group and cardiac insufficiency group received the intragastric administration of 2 mL/(kg·d) normal saline for 4 weeks. Before operation and 2,4, 6 weeks after operation, cardiac function was measured by cardiac ultrasound, and serum levels of Gal-3 and brain natriuretic peptide (BNP) were detected by ELISA. The mRNA expressions of Gal-3, collagen Ⅰ and Ⅲ in myocardial tissue were detected by real-time quantitative PCR, and the ratio of Ⅰ/Ⅲ was calculated. 6 weeks after operation, Masson staining was used to observe the histopathology of myocardial infarction region, and the protein expressions of Gal-3, collagen Ⅰ and Ⅲ were detected by Western blot. Results After 4 weeks of administration, the heart function of the MCP group was significantly improved compared with the cardiac insufficiency group (P＜0.01). The serum Gal-3 in cardiac insufficiency group was higher than that in sham operation group (P＜0.05), and serum Gal-3 in MCP group was significantly lower than that in cardiac insufficiency group (P＜0.05). Correlation analysis showed that left ventricular ejection fraction was negatively correlated with serum Gal-3 (r＝－0.841, P＝0.009), and left ventricular end-diastolic diameter was positively correlated with serum Gal-3 (r＝0.905, P＝0.002), in cardiac insufficiency group. Compared with cardiac insufficiency group, the mRNA expression of Gal-3, collagen Ⅰ and Ⅲ in MCP group was significantly decreased (P＜0.05). Under optical microscope, cardiac insufficiency group showed myocardial cell disorder, part of myocardial cell necrosis, edema, acollagen deposition and inflammatory cell infiltration; MCP group showed myocardial fiber thickening, arranging in a slightly tidy order. Protein expressions of Gal-3, collagen Ⅰ and Ⅲ in the infarcted myocardium of cardiac insufficiency group were significantly higher than those in MCP group and sham operation group. Correlation analysis showed that Gal-3 in infarction region was positively correlated with collagen Ⅲ in cardiac insufficiency group (r＝0.793, P＝0.019). Conclusion Gal-3 plays a key role in the progressions of ventricular remodeling and myocardial fibrosis in heart failure.

Abstract:Aim The aim of the study was to investigate the relationship between the ApoC3 rs5128 polymorphism and plasma lipid levels and the severity of coronary stenosis in the coronary heart disease (CHD) patients with different body mass index (BMI) in Chinese Han population. Methods Three hundred and twelve CHD patients were divided into healthy weight group(205 patients) and overweight/obese group(107 patients). Physiological, biochemical and coronary angiographical data were collected for all patients. The severity of coronary stenosis was assessed by the Gensini scoring system. Genome DNA was extracted from peripheral blood leucocytes and the genotypes of the ApoC3 rs5128 polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism method. Results The overweight/obese patients had higher weight, BMI, prevalence of hypertension, triglyceride (TG), lipoprotein (a), TG/high-density lipoprotein cholesterol (HDLC), total cholesterol (TC)/HDLC, low-density lipoprotein cholesterol (LDLC)/HDLC and apolipoprotein B100 (ApoB100)/apolipoprotein AI (ApoAⅠ), and lower HDLC and ApoAⅠ than the patients with healthy weight (P<0.05). In healthy weight group, the G carriers had higher prevalence of hypertension than the patients with the CC genotype (P<0.05). In overweight/obese group, the G carriers had higher levels of TG and TG/HDLC than the patients with the CC genotype (P<0.05). In healthy weight group and overweight/obese group, there were no significant differences in the distributions of the genotypes or alleles of the rs5128 polymorphism among the tertiles of the Gensini scores. Conclusion The ApoC3 rs5128 polymorphism is significantly associated with plasma TG and TG/HDLC levels, but not with the severity of CHD.

Abstract:Aim To study the relationship between DNA methylation level of intercellular adhesion molecule 1(ICAM-1) and atherosclerosis (As) occurrence, development and changes of blood lipids. Methods The atherosclerosis patients (100 patients from Hui and Han ethnic with As) were confirmed by carotid artery Doppler ultrasound and the serum lipids were measured by ADVIA 2400 automatic biochemistry analyzer, ICAM-1 mRNA expression was determined by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The methylation status of ICAM-1 gene promoter region was examined using nest touch down methylation specificpolymerase chain reaction (nt-MSP). Results Compared with As patients from Han ethnic, ICAM-1 mRNA expression levels were promoted in Hui ethnic (P<0.001), and the levels of ICAM-1 promoter methylation was decreased in Hui ethnic (P<0.001). Compared with As patients from Hui ethnic, triglycerides (TG) concentrations was promoted in As patients from Han ethnic(P<0.001), and was negatively correlated with ICAM-1 promoter methylation (r=－0.5783, P<0.001). Conclusion ICAM-1 DNA hypomethylation is related to the occurrence and development of As and the changes of serum lipids in peripheral blood mononuclear cells of Hui patients.

Abstract:Aim To find the causes of clopidogrel resistance caused by high blood glucose from the view of platelet energy metabolism by detection of molecular markers. Methods About 122 patients with coronary artery disease (CAD) accompanying hypertension (HPT) were randomly analyzed. The patients were divided into low response group (LRG) and response group (RG) according to the inhibition of their platelet through the way of ADP inhibition rate in thrombelastogram (TEG). 19 cases (hyperglycemia group)were randomly selected from the group of LRG with hyperglycemia, and 20 cases (no hyperglycemia group) were randomly selected from the group of RG without diabetes or with normal glucose tolerance test. Fresh platelets were isolated for ATP and mitochondrial membrane potential (Δψm) analysis. ATP contents were determinated by luciferin/luciferase luminometric method, and the flow cytometry technique was adopted to evaluate Δψm. In all participants correlation between platelet ATP content, Δψm and other variables was analyzed by a multivariable stepwise regression. Results Platelet ATP contents were significantly higher in hyperglycemia group (4.369±2.174 mmol/g) than in no hyperglycemia group (1.628±0.452 mmol/g； P<0.001). Interestingly, Δψm was markedly decreased in patients of hyperglycemia group (0.484±0.118) compared with no hyperglycemia group (2.381±0.194; P<0.001). For whole subjects, a liner stepwise regression showed that plasma glycated hemoglobin A1c (HbA1c) level was positively correlated to platelet ATP content (β=1.235; P=0.000), and negatively correlated to Δψm (β=－0.54; P=0.000). Although, the age of the patients was involved in the regression equation, but significant correlation (β=0.03; P=0.006) was found between Δψm and HbAlc instead of age. Conclusion High blood glucose leads platelet to produce more ATP, resulting in increased platelet activity, making it easier for patients with high blood glucose to develop Clopidogrel resistance (CR). At the same time, high blood glucose reduces the Δψm of platelets, promoted early apoptosis, indirect CR may be induced.

Abstract:Aim To investigate the correlation between non-high density lipoprotein cholesterol level and severity coronary heart disease(CHD). Methods 522 cases of coronary angiography were retrospectively analyzed, according to the results of coronary angiography combined with clinical features, electrocardiogram and myocardial enzyme, which were divided into non-CHD group, angina pectoris group, myocardial infarction group. The average age is 60.00±10.02 years. Gensini score was used to evaluate the degree of coronary artery lesions in patients with coronary heart disease, the clinical data of all patients were collected, and the serum lipid levels were measured and non-high density lipoprotein cholesterol was calculated. The correlation between non-high density lipoprotein cholesterol and coronary heart disease was analyzed. Results Gensini levels had statistically significant differences in the three groups (P<0.05); In angina pectoris group, non-high density lipoprotein cholesterol level and Gensini score are positively correlated (r=0.130, P=0.022); In myocardial infarction group, non-high density lipoprotein cholesterol level and Gensini score are positively correlated (r=0.213, P=0.048); Logistic regression analysis showed that age, gender and non high density lipoprotein cholesterol level were risk factors for coronary heart disease (P<0.05). Conclusion Non-high density lipoprotein cholesterol is an important index to reflect the condition of patients with coronary heart disease.

Abstract:Aim To investigate the relation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and SYNTAX score in postmenopausal women with coronary atherosclerotic heart diseases (CAD). MethodsA cohort of 180 postmenopausal women was enrolled in this study, who was diagnosed as CAD by coronary angiography. The patients were categorized in three groups based on the admission MHR level:low MHR group(MHR＜0.28, n=59),moderate MHR group(0.28≤MHR≤0.43, n=61), high MHR group(MHR＞0.43,n=60). Spearman correlation and multiple linear regression were used to describe the linear association between MHR and SYNTAX score. Results The SYNTAX scores of high MHR group (25±13) were higher than low MHR group (18±13) and moderate MHR group (19±12) (P=0.003). The counts of white blood cells, counts of neutrophil and serum levels of C-reactive protein in high MHR group were higher than those in low MHR group and moderate MHR group (P＜0.001 for all comparisons). Spearman correlation analysis showed MHR was correlated with SYNTAX score(r=0.263,P＜0.001). The result of multiple linear regression indicated that SYNTAX score was affected by MHR(F=4.777,P=0.031). Conclusion This study demonstrated that MHR of postmenopausal women with CAD was significantly positively correlated with SYNTAX score. MHR may be used to predict coronary artery lesion of postmenopausal women with CAD.

Abstract:Aim To investigate the relationship between body mass index (BMI) and arterial stiffness. Methods 6143 cases with 2006-7,8-9,0-2011 body examination and brachial-ankle pulse wave velocity (BaPWV) of 2010-2011 were analyzed. The average age was 49.68 years old. Among them, 4230 cases (68.9%) were male. All of them were divided into four groups according to the BMI locus, the BMI locus and arteriosclerosis were tested by χ² and the multiple factors logistic regression analysis was conducted to observe the effect of BMI locus on arteriosclerosis. Results With the increase of BMI trajectory, arteriosclerosis detection rate increased gradually, the trajectory of arteriosclerosis detection rates were 52.4%, 63.3%, 67.9%, 70.1%; in a multivariate logistic regression analysis adjusted for age, gender and other confounding factors, compared with the low stable group, the other three groups (ABI＜0.9 value of OR 95%CI) were 1.34(1.08～1.66),1.57(1.16～2.13),1.77(1.13～2.79). Conclusion High BMI locus is a risk factor for atherosclerosis and is independent of other risk factors for target organ damage.

Abstract:Aim To illustrate patterns of statin therapy in patients with Acute Myocardial Infarction (AMI) in central-western urban China from 2001 to 2011, and identify factors affecting the use of statins. Methods A two-stage random sampling design was used to create a representative sample of patients who were admitted to hospital for AMI in central-western urban China in 1,6 and 2011. In the first phase, simple random-sampling procedure was used to identify participating hospitals. In the second phase, patients were selected from each sampled hospital in above 3 years through a systematic sampling approach. Medical records were centrally abstracted to get patients’ information. The findings were weighted for each year to represent the overall situation. Binary logistic regression analysis was used to identify factors related to the use of in-hospital statins. Results 31 randomly sampled urban hospitals in central-western China participated in the study, and 3 354 AMI admissions were included in analysis. There has been a significant increase in the use of statin therapy, the proportion of which was 19.7% in 1,9% in 2006, and 91.1% in 2011. Overall, statin use significantly increased among all low density lipoprotein-cholesterol (LDLC) groups during 10 years. Lovastatin was the most common stain in 2001 and it turned to be atorvastatin in 2011. Logistic regression analysis showed that patients who smoke (OR=1.36; 95% CI 1.07~1.73, P=0.011) were more likely to be treated with statin therapy. Conclusion During the past decade, the use of statin therapy has dramatically increased in central-western China. However, a lot still needs to be done to optimize the use of statin therapy among AMI patients.

Abstract:Plasma low density lipoprotein (LDL) and high density lipoprotein (HDL) are important biochemical indicators of clinical cardiovascular disease (CVD). Some disorders of lipid metabolism, such as obesity, diabetes mellitus, hypertension and hyperlipidemia, especially atherosclerosis, are risk factors for CVD. Many new studies have demonstrated abnormalities of plasma LDL and HDL subunits in patients with these diseases, and their clinical significance is greater than the overall abnormalities of LDL and HDL. Abnormal subunits of plasma LDL and HDL have been extensively studied and paid attention to as a clinical indicator of CVD. The purpose of this paper is to discuss the advances in clinical significance and detection research of plasma LDL and HDL subunits.

Abstract:The incidence of hypertension is increasing year by year in the whole world. It has become the consensus of the medical community to study the pathogenesis of hypertension. The insufficiency of energy supply, oxidative damage and abnormal signal transduction caused by mitochondrial dysfunction and mitochondrial gene mutation are the risk factors of hypertension. Understanding the relationship between mitochondrial dysfunction and hypertension will provide new ideas for the research and treatment of hypertension. This paper has discussed mitochondrial function, mitochondrial dysfunction and the relationship between mitochondrial dysfunction and hypertension in great detail.

Abstract:Atherosclerosis is a common cardiovascular disease, which is the most important pathological basis of cardiovascular and cerebrovascular diseases. In recent years, the incidence and mortality of atherosclerosis has increased significantly, which has become an urgent problem to be solved. Salusins is a new vasoactive peptide which plays an important role in the formation of atherosclerosis. A large number of studies have shown that salusins is highly expressed in atherosclerotic plaques, which plays an important role in the development and progression of atherosclerosis and becomes a new therapeutic target. In this paper, the latest research progress in this field was reviewed, and the research status of atherosclerosis and salusins both domestic and overseas was discussed.

Abstract:It is known that vascular calcification is a regulated ectopic mineral deposition,which is a common characteristic of chronic inflammatory disorders, such as type 2 diabetes mellitus, atherosclerosis, and chronic kidney disease.Vascular calcification is closely related to the morbidity and mortality of cardiovascular diseases. Vascular calcification is as a state of chronic inflammatory disorders, and inflammatory factors may play an important role in the regulation of vascular calcification. As a kind of non-encoding small RNA, microRNA, many studies have confirmed that it can be through the regulation of vascular smooth muscle cell phenotype conversion, calcium and phosphorus homeostasis, local and systemic expression of inflammatory factors to cause the occurrence and development of vascular calcification. Recently, various kinds of microRNA have been found. In this review, the focus will be on the relationship between inflammation and vascular calcification, the role of inflammation-related microRNA in vascular calcification by regulating the expression of inflammatory factors, which will provide novel concept for future studies on mechanisms of vascular calcification, prevention and treatment strategies of vascular calcification in clinic.

Abstract:Anticoagulant therapy is recommended for most patients with nonvalvular atrial fibrillation (NVAF) to reduce the risk of stroke and systemic embolism. Temporary interruption of oral anticoagulant drugs (OAC) in preparation for a procedure, is frequently necessary, most often to mitigate bleed risk with surgical or invasive procedures in these patients. In recent years, a lot of clinical studies related to periprocedural management of anticoagulant therapy for NVAF patients have been performed by specifical addressing:①whether or when anticoagulant therapy should be interrupted; ②whether or how anticoagulant bridging with a parenteral agent should be performed; ③when and how anticoagulant therapy should be restarted. Research status of periprocedural anticoagulation in NVAF patients will be reviewed in this article.