Abstract:Statins is an effective drug with proven benefits in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However,several clinical researches indicate that the long-term use of statins may increase the risk of new-onset diabetes mellitus (NODM). Pitavastatin, as a newest form of statins, is called “super statin” because of its better safety and tolerability. The correlation between pitavastatin and NODM risk is inconsistent. Some research indicated that pitavastatin had no negative effect on glucose metabolism, and might even improve insulin resistance. While, some other researchers consider that increased NODM risk is a kind of effect for all statins, including pitavastatin. This review summarizes the research progress on the effect of pitavastatin and glucose metabolism.

Abstract:Aim To investigate the effect of overexpression of omentin on collagen content in aorta of diabetic atherosclerosis rats. Methods 60 one-month-old male Wistar rats were randomly divided into normal control group (NC group; n＝8) and experimental group (n＝52). The experimental group was fed with high-fat and high-sugar diet and injected 2% streptozotocin (30 mg/kg) into tail vein to establish diabetic rat model. The diabetic rats were fed with vitamin D3 (0,0 IU/kg) for 16 weeks to establish a diabetic rat model with arteriosclerosis. 24 diabetic atherosclerosis rats were randomly divided into diabetic atherosclerosis group (DAC group; n＝8), diabetic atherosclerosis plus empty virus group (DAC＋E group; n＝8) and diabetic atherosclerosis plus omenin group (DAC＋O group; n＝8). 150 μL adeno-associated virus carrying human omentin gene ITLN1-AAV9 and 150 μL virus carrying empty plasmid were injected into DAC＋O group and DAC＋E group via tail vein, respectively, and equivalent physiological saline was injected into NC group and DAC group. The rats were fed with high-fat diet for 4 weeks. The serum and liver omentin and blood lipid levels were measured. The aorta was taken for HE staining. Quantitative real-time polymerase chain reaction was used to determine the contents of collagen Ⅰ, Ⅲ, matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA. Protein contents of collagen Ⅰ, Ⅲ, MMP-2 and MMP-9 in aorta were determined by Western blot. The content of aortic superoxide dismutase (SOD) was determined by xanthine oxidase method. Aortic malondialdehyde (MDA) levels were measured by thiobarbituric acid condensation method. Results (1)Compared with NC group, the level of serum omentin in diabetic atherosclerosis rats decreased significantly. After intravenous injection of adeno-associated virus carrying human omentin gene, in DAC＋O group, the serum and liver levels of human omentin were 101.0±0.2 and 98.3±1.9 μg/L, respectively. Human omentin was not detected in corresponding tissues of other groups. (2)Compared with DAC group, serum lipid profile and aortic MDA in DAC＋E group and DAC＋O group decreased significantly, while SOD increased, but there was no significant difference between the latter two groups. (3)In DAC group, aortic intima was partially exfoliated, smooth muscle was proliferated, local hyalinization and calcification were observed. In DAC＋O group, the intima was intact, the local wall was thickened, the degree of smooth muscle proliferation and calcification was significantly improved compared with DAC group. (4)Compared with DAC＋E group, the expressions of collagen Ⅰ and Ⅲ mRNA and collagen Ⅲ protein in DAC＋O group decreased significantly. Compared with DAC＋E group, there was no significant difference in the expressions of MMP-2, MMP-9 mRNA and protein in DAC＋O group. Conclusion In diabetic atherosclerosis rats, overexpression of human omentin can reduce the expression of collagen Ⅲ in aorta, alleviate atherosclerosis, and has no significant effect on oxidative stress level.

Abstract:Aim To explore the mechanism of curcumin trinicotinate (CurTn) regulating vascular contractility and its effect on phenotype regulation of vascular smooth muscle cell (VSMC). Methods C57BL/6 mice were intragastrically administered with 50 mg/(kg·d) CurTn for 6 weeks. The thoracic aorta of the mice was taken after 6 weeks of continuous administration. The contractility of thoracic aorta was examined by tissue myograph system, and the levels of contractile proteins were detected in vascular tissues. VSMCs were treated with 10 μmol/L CurTn for 24 h; Western blot was used to detect the expressions of phenotypic related factors; The proliferation and migration of VSMC were observed by methyl thiazolyl tetrazolium staining and scratch assay; Oil red O staining and high performance liquid chromatography were used to analyze the phagocytosis of low density lipoprotein (LDL) by VSMC. Results The contractility of thoracic aorta vessel was enhanced and the expression of contractile protein in vascular smooth muscle tissue was increased in curTn-treated mice. Our results also showed that CurTn increased the expressions of myocardin and contractile-specific marker proteins α-actin and SM22α in VSMC, and decreased the level of osteopontin, a proliferative-specific marker. Further study found that the migration and proliferation of VSMC were inhibited by CurTn. LDL-treated VSMC was used to detect the effects of CurTn on lipid uptake, and it found that CurTn inhibited the phagocytosis of VSMC. Conclusion CurTn enhances vascular contractility, probably by promoting the contractile phenotype of VSMC and preventing its proliferative phenotype.

Abstract:Aim To investigate the therapeutic effect of tissue plasminogen activator(t-PA) gene modified umbilical cord blood endothelial progenitor cells (EPCs) transplantation on acute myocardial infarction in rats. MethodsEPCs were expanded in vitro,the slow virus expression vector of t-PA gene was transfected into endothelial progenitor cells to establish rat myocardial infarction model,the experiment was randomly divided into 4 groups:PBS solution group, EPCs group transfected with empty vector, simple EPCs group and EPCs group transfected with t-PA gene. Transplantation was started after acute myocardial infarction 3h in rats, t-PA EPCs group, EPCs group, and empty vector EPCs group were injected with T-PA gene-transfected EPCs, EPCs, and empty vector EPCs. Four weeks after transplantation, cardiac function were evaluated by echocardiography and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) expression level was detected,then the expression levels of vascular endothelial growth factor(VEGF)and matrix metalloproteinase-2/matrix metalloproteinase-9 (MMP-2/MMP-9) and Tissue inhibitor of metalloproteinase(TIMP) in myocardial tissue were detected by Western-blot. Eight hours after transplantation, the expression of t-PA, D-Dimer, fibrin degradation products(FDP), plasminogen activator inhibitor 1 (PAI-1) and fibrinogen (Fib) in serum was detected by ELISA. Results Compared with PBS solution group, empty carrier EPCs group and simple EPCs group,the effect of t-PA gene modified EPCs was the most significant in improving various parameters of cardiac function in rats with acute myocardial infarction. The expression level of NT-Pro-BNP in t-PA EPCs group was significantly lower than that in other groups. The expression level of VEGF and TIMP in t-PA EPCs group was significantly higher than that in other groups. On the contrary, the expression level of metalloproteinase (MMP-2/MMP-9) was significantly lower than that of other groups. The expressions of t-PA and D-dimer in t-PA EPCs group were significantly higher than those in other groups, while PAI-1 and fibrinogen were significantly lower than those in other groups. Conclusions t-PA gene modified EPCs transplantation can effectively treat acute myocardial infarction in rats. Its specific therapeutic effect is related to improving cardiac function, promoting angiogenesis, inhibiting ventricular remodeling, inhibiting thrombosis or increasing thrombolysis.

Abstract:Aim To investigate the effects and mechanisms of quantum lipid-lowering instrument on lipid regulation. Methods High fat diet and 10% fructose were used to establish a rat model of hyperlipidemia. The output power of the quantum lipid-lowering instrument was 70 μW/cm², and the treatment time was 5~10 minutes for each time,1~2 times a day. Elisa kit was used to detect serum lipid levels and Western blot was used to measure the expressions of key protein in lipid metabolic and inflammatory pathways. Results Quantum lipid-lowering instrument can improve the disorder of blood lipid metabolism, regulate blood lipid balance, reduce inflammation, alleviate liver function damage, alleviate oxidative damage, increase the activity of lipid metabolism-related enzymes, and inhibit the activity of fatty acid synthase which is caused by hyperlipidemia. Western blot showed that Quantum lipid-lowering instrument could alleviate inflammation by regulating the expression levels of nuclear factor κB (NF-κB), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6);modulate the expression of peroxisome proliferators-activated receptors α (PPARα) which could improve lipid metabolism;regulate the sterol-regulatory element binding proteins 2 (SREBP-2) pathway to increase low-density lipoprotein receptor (LDLR) protein expression, alleviate lipid metabolism disorders, and regulate cholesterol and triglyceride levels. Conclusion Quantum lipid-lowering instrument has obvious effect of lipid regulation, and can be used as an assisted clinical instrument for lowering lipid.

Abstract:Aim To study the effect of Notch1/Hes1 pathway activation on the cardiomyocyte hypertrophy induced by high glucose (HG), and observe its role in oxidative stress. Methods Primarily cultured rat cardiomyocytes were used in the study. The cell surface areas of the cardiomyocytes were measured by an image analysis system. The cell protein content was detected by BCA method. The expression levels of Notch1, Hes1, superoxide dismutase 1(SOD1) and induction nitric oxide synthase(iNOS) were determined by RT-qPCR and Western blot. Related kits were used to measure the content of malondialdehyde(MDA) and mtric oxide(NO) in cardiomyocytes. Results Compared with control group, the cell surface areas and total protein content of the cardiomyocytes were significantly increased (P<0.05), the expression levels of Notch1 and Hes1 were significantly decreased (P<0.05), the levels of MDA, NO and iNOS were significantly increased (P<0.05), and the expression of SOD1 was greatly decreased (P<0.05) in HG-induced cardiomyocytes. Notch1 activation suppressed HG-induced cardiomyocyte hypertrophy and the levels of oxidative stress (P<0.05). These effects of Notch1 activation were abolished by Notch1 gene interference (P<0.05). Conclusion Notch1 activation reduces HG-induced cardiomyocyte hypertrophy by decreasing oxidative stress in cardiomyocyte.

Abstract:Aim To evaluate the prognostic value of plasma interleukin-6 (IL-6) and interleukin-27 (IL-27) level in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods Patients with STEMI diagnosed first time and underwent PCI in People’s Hospital of Xinjiang Uygur Autonomous Region were consecutively enrolled from January 2015 to December 2016. Clinical data and blood samples before PCI were obtained from all patients. Plasma levels of IL-6 and IL-27 were measured by enzyme-linked immunosorbent assay. The patients were divided into two groups based on the occurrence of major adverse cardiovascular events (MACE) during 1-year follow-up after STEMI diagnosis. Logistic regression analysis was performed to evaluate the relationship between plasma IL-6 and IL-27 levels and the occurrence of MACE. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive values of IL-6 and IL-27 on the occurrence of MACE. Results Among 287 patients with STEMI, 179 (62.4%) were males and the age was 61.37±9.3,7 (19.9%) had MACE. Compared with controls, patients in MACE group were older with higher Gensini score, higher plasma IL-6 and IL-27 levels. The prevalence of smoking, diabetes, and two- or multi-vessel coronary artery disease were higher in MACE group in comparison to controls. Logistic regression analysis demonstrated that IL-6 (OR＝1.2,5%CI was 1.50～2.15, P＜0.001) and IL-27 (OR＝1.4,5%CI was 1.11～1.42, P＜0.001) were significantly independent predictors of MACE in STEMI patients undergoing PCI. The area under the ROC curve of IL-6 and IL-27 for predicting MACE were 0.701 and 0.690, respectively. Conclusion Plasma IL-6 and IL-27 levels were independent risk predictors for identifying the MACE of 1-year follow-up in patients with STEMI underwent PCI, indicating that they may help to assess the clinical outcomes for us.

Abstract:Aim To evaluate the effects of ezetimibe co-administered with statins vs statins dose-doubling on major adverse cardiovascular events in patients with coronary heart disease systematically, in order to provide evidence-based reference for clinical use. Methods The pertinent randomized controlled trials (RCTs) about ezetimibe co-administered with statins trail group and statins dose-doubling control group in the treatment of coronary heart disease were retrieved from The Cochrane Library, PubMed, Embase, CNKI, CSTJ, CBMdisc and Wan fang Database. The quality of included studies were evaluated according to modified Jadad quality scale after extracting data. Meta-analysis was performed by using RevMan 5.3 statistical software. Results A total of 30 RCTs were included,involving 4 757 patients. The results of Meta-analysis showed that compared with double-dose statins, ezetimibe-plus-statins markedly decrease major adverse cardiovascular events(P=0.03), angina(P＜0.001) and myocardial infarction(P＜0.001); the incidence of cardiac death, revascularization, heart failure and stroke had no significant difference in two groups; ezetimibe-plus-statins significantly decrease adverse reactions, such as transaminase elevation(P＜0.001), creatine kinase elevation(P=0.02), and muscle pain, muscle weakness and other muscle injuries(P＜0.001). Meta-analysis in subgroup was studied according to the kinds and dosage of statins and follow-up time, compared with atorvastatin 40 mg, ezetimibe 10 mg plus atorvastatin 20 mg showed more advantages in reducing the incidence of major adverse cardiovascular events and myocardial infarction than other subgroups. However, no effect was found on the results between a long follow-up time (≥6 months) with a short follow-up time (≤3 months). Conclusions For patients with coronary heart disease, statins combined with ezetimibe has a significant benefit in myocardial infarction and angina compared with double dose statins, but the benefit of cardiac death and stroke were not found. The incidence of adverse reactions is significantly reduced.

Abstract:Aim To explore the relationship between serum bilirubin and the severity of coronary artery lesion, prognosis in patients with angina. Methods This study included 486 continuous angina patients meeting the conditions from January 1,3 to December 1,5. The subjects included 292 males and 194 females, with an average age of (61.4±13.2) years. On the day before discharge, fasting venous blood was drawn to detect total bilirubin. Coronary angiography was retrospectively analyzed and the coronary artery lesions were scored using the SYNTAX scoring system. In this study, prospective follow-up was performed. The initial event was PCI and the end event was major adverse cardiovascular events (MACE). The follow-up deadline was December 1,7. Multivariate logistic regression was used to analyze the relationship between serum bilirubin and SYNTAX scores. The Kaplan-Meier method was used to estimate the survival rate. The log-rank test was used to compare the two survival curves. The relationship between serum total bilirubin and MACE was analyzed by multivariate Cox proportional hazards regression. Results Multivariate logistic regression analysis showed that male, age, type 2 diabetes mellitus, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) and bilirubin were independent factors for the moderate-to-high SYNTAX score. MACE occurred in 38 patients of the low bilirubin group and in 25 patients of the hyperbilirubin group. There was significant difference in MACE-free survival curve between the two groups (χ²=4.785, P=0.029). Multivariate Cox regression analysis showed that male, age, bilirubin and SYNTAX scores were independent factors for the occurrence of MACE. Conclusion Serum bilirubin is an important factor affecting the degree of coronary artery lesion and long-term prognosis in PCI patients with angina.

Abstract:Aim To evaluate the value and correlation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and homocysteine (Hcy) combined detection for coronary atherosclerotic plaque in patients with coronary heart disease (CHD). Methods According to clinical classification, 188 patients with CHD were divided into 2 groups:stable angina pectoris (SAP) group (n＝106), acute coronary syndrome (ACS) group (n＝82); Those who had normal coronary angiography at the same time were selected as control group (n＝90). Serum levels of NT-proBNP, Hcy and high-sensitivity C-reactive protein (hs-CRP) were measured. According to the results of coronary angiography, Gensini score was calculated. Plaque component index was detected by intravascular ultrasound. Correlations between NT-proBNP, Hcy levels and Gensini score, plaque composition index were analyzed by Pearson correlation analysis. Relationship between NT-proBNP, Hcy levels and vulnerable plaques was analyzed by Logistic regression analysis. The values of NT-proBNP and Hcy in predicting vulnerable plaques were evaluated by the receiver operating characteristic (ROC) curve area under curve (AUC). Results There were significant differences in the concentrations of NT-proBNP, Hcy and hs-CRP among the 3 groups (P＜0.05), and all of them were ACS group＞SAP group＞control group (P＜0.05). The Gensini score, the ratio of necrotic core (NC), vascular remodeling index (VRI) and plaque eccentricity index (PEI) in group ACS were significantly higher than those in SAP group (P＜0.05). The levels of NT-proBNP and Hcy were positively correlated with Gensini score and plaque NC ratio, VRI and PEI (all P＜0.05). Multivariate Logistic regression analysis showed that serum NT-proBNP and Hcy levels were independent risk factors for vulnerable plaques in patients with CHD (all P＜0.05). The AUC values of NT-proBNP and Hcy in predicting coronary vulnerable plaques were 0.764 (95%CI 0.729~0.803, P＝0.021), 0.779 (95%CI 0.742~0.814, P＝0.015). When NT-proBNP and Hcy were combined, the AUC of predicting coronary vulnerable plaques was 0.886 (95%CI 0.823~0.951, P＝0.004). Conclusion Combined detection of serum NT-proBNP and Hcy can effectively assess coronary atherosclerotic plaques in patients with CHD.

Abstract:Aim To investigate the plasma apelin-12 level in the subjects with type 2 diabetes mellitus(T2DM)and its relationship with blood glucose. Methods 41 T2DM patients who were hospitalized in the department of endocrinology of civil aviation general hospital were selected from January 2012 to June 2015, and 44 healthy subjects were enrolled as control group. The patients with T2DM were divided into two groups including one group (21 persons) complicated with hypertension, cardiovascular and cerebrovascular disease and another group (20 persons) without complications for subgroup analysis. The level of apelin-12 was measured by enzyme linked immunosorbent assay. Glycosylated hemoglobin (HbA1c), cholesterol, triglyceride, low density lipoprotein, fasting blood glucose, 2-hour postprandial glucose (2hPG) and C peptide were determined in T2DM group and control group. The correlation between apelin-12 and clinical indicators was analyzed. Results (1) The content of apelin-12 was significantly lower in the T2DM group than in control group(t=2.70, P=0.01). (2)Subgroup analysis showed that there was no significant difference in plasma apelin-12 level between T2DM with cardiovascular and cerebrovascular diseases and T2DM without complications (t=－0.44, P=0.67). (3) With stepwise multiple regression analysis, taking apelin-12 as dependent variable, and age, body mass index, blood pressure, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, HbA1c, fasting blood glucose, 2-hour postprandial blood glucose, fasting C-peptide and 2-hour postprandial C-peptide were independent variables, fasting blood glucose was associated with apelin-12 in T2DM patients(B=－0.12, β=－0.42, t=－2.03, P=0.04).Conclusion Plasma apelin-12 levels were significantly lower in patients with T2DM and were negatively correlated with fasting blood glucose.

Abstract:Liver X receptors (LXRs) are nuclear factors and play important roles in the regulation of cholesterol homeostasis in the body. LXRs regulate cholesterol metabolism in different tissues through regulating their target genes. LXR agonists can promote the reverse cholesterol transport in order to inhibit atherosclerosis, and have potential therapeutic effects on cardiovascular diseases. In this paper, the new LXR agonists in recent years are reviewed for their anti-atherosclerotic effects from different sources, characteristics and mechanisms.

Abstract:C1q/TNF-related protein-6 (CTRP6) is a member of the CTRP superfamily. Recently, researchers have highlighted CTRP6 as a novel adipokine that play an important role in obesity and insulin resistance (IR). Exploring the biological function and molecular mechanism of CTRP6 in adipocytes may provide a new approach to obesity-related metabolic diseases. This paper mainly reviews the research progress of the structure, distribution of CTRP6, and its biological function in the pathogenesis of IR.

Abstract:High density lipoprotein (HDL) can transfer cholesterol from foam cells to the liver and metabolize it into bile and excreted into intestinal tract, finally exhaust out of body, then it produces an anti-atherosclerosis effect, which is called HDL's reverse cholesterol transport (RCT). Therefore, how to increase the concentration of HDL and promote the function of HDL to give full play to its anti-atherosclerosis function are becoming a research hotspot in recent years. However, studies have shown that simple elevation of HDLC level has no significant clinical effect, revealing the complexity of HDL function. Therefore, it is necessary to systematically review the molecular structure, synthesis and metabolism of HDL, and re-recognize the molecular biological basis of its RCT function, so as to provide theoretical support for further research on the RCT function of HDL.

Abstract:IgAN is the most common primary glomerular disease in China. It can occur at any age and progress chronically. Current data show that about 20%~40% of patients develop to end-stage kidney in 10~20 years. There are many factors contributing to the progress of IgAN. In addition to the recognized immune factors, many metabolic factors such as body mass index, insulin resistance and hyperuricemia have been reported in recent years, which are also related to the progress of IgAN. IgAN is not uncommon in patients with high BMI and kidney diseases, which are not all obesity-related nephropathy. This paper reviews the correlation between high BMI index and IgAN.