Abstract:Atherosclerosis is an important pathological basis of cardiovascular and cerebrovascular diseases. Endothelial cells lining blood vessels are a barrier with selective permeability between blood vessel wall and blood flow, and play an important role in maintaining homeostasis of blood vessels. Dysfunction of vascular barrier function is one of the important steps in the development of atherosclerosis. Recent studies have shown that hemodynamics can significantly affect the endothelial barrier function. Abnormal blood flow pattern such as disturbed flow and oscillatory flow can significantly change the permeability of vascular endothelium and even induce breaches of the arterial intima. By focusing on the latest research results on material exchange inside and outside of endothelial cells and arterial intimal rupture, the study reviews the influence of hemodynamic changes on the function of vascular endothelial cell barrier, and discusses the fields worthy of further study, so as to provide a new idea for further elucidating the mechanism of the occurrence and development of atherosclerosis and the selection of effective prevention and treatment strategies.

Abstract:Aim To study the molecular mechanism of heart high-expressing gene hhole on regulating the transcriptional activity of cardiac hypertrophic signaling molecule ANF. Methods Bioinformatics online software was used to analyse the molecular structure of hhole protein. Several mutants of the recombinant plasmid pCMV-tag2B-hhole were constructed by restriction digestion and site-directed mutagenesis. The mutant and wild-type recombinant plasmids were transfected into HEK293 cell line respectively to determine the transcriptional activity of luciferase reporter gene ANF. Results The bioinformatics analysis reveals that hhole protein contains a binding site of ERK (D-domain) and proline-rich SH3 binding motifs. Four mutants of the recombinant plasmid pCMV-tag2B-hhole have been constructed by restriction digestion and three mutants have been constructed by site-directed mutagenesis. The report assay showed that recombinant plasmids pCMV-tag2B-TD and pCMV-tag2B-hhole could suppress strongly the transcriptional activities of ANF. Conclusion The binding site of ERK-D-domain of hhole protein played a crucial role in inhibiting the transcriptional activities of hypertrophic signal molecule ANF.

Abstract:目的 研究棕榈酸(PA)对内皮细胞株EA.hy926胆固醇代谢的影响,检测胆固醇流出、胆固醇胞内转化、脂蛋白摄入以及信号通路相关基因表达的变化。方法 体外培养内皮细胞株EA.hy926,分为白蛋白(ALB)对照组和PA处理组。采用实时荧光定量PCR法检测ATP结合盒转运体A1(ABCA1)、ABCG1、27-羟化酶、清道夫受体A1(SR-A1)、SR-B1、CD36、凝集素样氧化低密度脂蛋白受体1(LOX-1)、肝X受体α(LXRα)、过氧化物酶体增殖物激活受体γ(PPARγ)的表达变化。结果 和ALB对照组相比,10、20、30 μmol/L PA处理组ABCG1 mRNA水平显著下降(P＜0.01),20、30 μmol/L PA处理组CD36、LOX-1 mRNA水平显著升高(P＜0.05)。与ALB对照组相比,10、20、30 μmol/L PA处理组LXRα mRNA水平显著下降(P＜0.1、P＜0.05、P＜0.1),10 μmol/L PA处理组PPARγ mRNA水平显著下降(P＜0.05)。而10、20、30 μmol/L PA处理EA.hy926细胞未显著影响ABCA1、SR-A1、SR-B1、27-羟化酶的表达。结论 PA能够改变内皮细胞EA.hy926细胞胆固醇流出和脂蛋白摄入相关基因的表达,其机制与LXRα和PPARγ信号途径有关。

Abstract:Aim To investigate the effects of Shensong Yangxin Capsule on the expression of IGF-1 and chemerin in myocardial cells. Methods Myocardial cells were isolated from SD rats and were divided into three groups. The normal group were routinely cultured, the I/R group were treated by hypoxia-reoxygenation to establish model of myocardial ischemia-reperfusion injury, the Capsule group were added final concentration of 320 μmol/L Shensong Yangxin Capsule pretreated for 24 hours before the model were established, and the expression of IGF-1 and chemerin in cardiomyocytes were recorded in different time. Results After 24 h, 36 h and 48 h treatment, the cell survival rate of the I/R group and the Capsule group were significantly lower (P<0.05) and the ROS level were significantly increased (P<0.05), the difference between the Capsule group and the I/R group were also statistically significant (P<0.05).After 48 h treatment, compared with the normal group, the ratio of G0/G1 phase cells in the I/R group and the Capsule group were increased (P<0.05), and the relative expression of IGF-1 and chemerin protein were increased significantly (P<0.05). The proportion of cells in the S phase and G2/M phase were decreased (P<0.05), and the difference compared between Capsule group and I/R group were also statistically significant (P<0.05). Conclusion Shensong Yangxin Capsule can inhibit the expression of IGF-1 and chemerin in cardiomyocytes, thereby improving the survival rate of cardiomyocytes, reducing the level of ROS and balancing the cell cycle, and exerting protective effects on myocardial ischemia-reperfusion injury.

Abstract:Aim To study the effects of melatonin (MT) on homocysteine (Hcy)-induced injury of coronary artery endothelial cells and clarify whether the mechanism is related to the activation of protein kinase B (Akt)/mammalian rapamycin target protein (mTOR) pathway. Methods Human coronary artery endothelial cells (HCAEC) were cultured and grouped. The control group was treated with DMEM without drugs, the Hcy group with DMEM containing 1 mmol/L Hcy, the MT group with DMEM containing 1 mmol/L Hcy and 5 μmol/L MT, and the MT+LY group with DMEM containing 1 mmol/L Hcy, 5 μmol/L MT and 10 μmol/L LY2942. Cell viability, cell apoptosis, cell cycle and the expression of p-Akt and p-mTOR were detected. Results Cell viability,Sü phase and G2/M phase ratio, the expression of Bcl-2, cyclinD1, p-Akt and p-mTOR in Hcy group were lower than those in control group, apoptotic rate, G0/G1 phase ratio, the expression levels of Bax and cleaved caspase-3 in Hcy group were higher than those in control group; cell viability,Sü phase and G2/M phase ratio, the expression levels of Bcl-2, cyclinD1, p-Akt and p-mTOR in MT group were higher than those in Hcy group, apoptotic rate, G0/G1 phase ratio, the expression levels of Bax and cleaved caspase-3 in MT group were lower than those in Hcy group; cell viability,Sü phase and G2/M phase ratio, the expression of Bcl-2, cyclinD1, p-Akt and p-mTOR in MT+LY group were lower than those in MT group, apoptotic rate, G0/G1 phase ratio, the expression levels of Bax and cleaved caspase-3 in MT+LY group were higher than those in MT group. Conclusion MT can reduce the apoptosis of HCAEC induced by Hcy, regulating Akt/mTOR pathway is one of the mechanisms responsible for MT reducing HCAEC injury.

Abstract:Aim To explore the improvement effects of Urocortin-I on myocardial monophasic action potential and oxidative inflammatory response in ischemia-reperfusion (I/R) myocardium by activatingAkt/GSK-3 β pathway. Methods Langendorff perfusion model of isolated myocardium was prepared and then divided into control group, I/R group, Urocortin-I group and Urocortin-I+LY group. The control group was given routine perfusion, I/R group was given routine preconditioning, Urocortin-I group was given Urocortin-I preconditioning, Urocortin-I+LY group was given Urocortin-I and LY2942 preconditioning before ischemia-reperfusion. The differences of myocardial enzymes, infarct size, monophasic action potential, inflammatory factors, oxidative stress products and Akt/GSK-3 β pathway molecules among the four groups were compared. Results Compared with the control group, the contents of LDH, CK-MB, TNF-α, IL-6, ICAM-1, ROS, MDA and the size of myocardial infarction significantly increased, while the levels of APA, APD50, APD90 and the expression of p-Akt, p-GSK-3β significantly decreased in the I/R group (P<0.05). Compared with the I/R group, the contents of LDH, CK-MB, TNF-α, IL-6, ICAM-1, ROS, MDA and the size of myocardial infarction significantly decreased, while the levels of APA, APD50, APD90 and the expressions of p-Akt, p-GSK-3β significantly increased in the Urocortin-I group (P<0.05). Compared with the Urocortin-I group, the contents of LDH, CK-MB, TNF-α, IL-6, ICAM-1, ROS, MDA and the size of myocardial infarction significantly increased, while the levels of APA, APD50, APD90 and the expressions of p-Akt, p-GSK-3β significantly decreased in the Urocortin-I+LYgroup (P<0.05).Conclusion Urocortin-I improves monophasic action potential and oxidative inflammation in I/R myocardium by activating Akt/GSK-3 β pathway.

Abstract:Aim To measure left atrial (LA) phase function and heart rate variability (HRV) in patients with asymptomatic diabetes by tissue Doppler echocardiography. The correlation between LA phase function and HRV was evaluated. Methods 158 patients with type 2 diabetes mellitus (diabetes mellitus group, n=158) with normal blood pressure and without clinical symptoms and 120 healthy persons with normal blood and pressure and without cardiovascular diseases (control group, n=120) were selected. Left atrial total emptying fraction (LATEF), left atrial passive emptyingvolum (LAPEF), left atrial active emptying fraction (LAAEF), global longitudinal strain (GLS), early diastolic velocity of left atrial strain rate and late diastolic velocity of left atrial strainrate were measured by tissue Doppler echocardiography. Standard diviation of NN intervals (SDNN), root mean square successive difference (rMSSD), percentage of adjacent R-R intervals that varied by more than 50 ms (p50NN), time domain HRV index and low frequency domain 24 h (LF), high frequency domain (HF) and total power (TP) were measured by multifunctional electrocardiograph. The difference of above indexes between diabetic group and control group were compared. Univariate and multivariate Logistic were used to evaluate the correlation between HRV and LATEF, GLS and other LA temporal functional indicators. Results LATEF (t=5.167, P<0.1) and LAPEF (t=21.486, P<0.1) were significantly lower in the diabetic group than in the control group. LAAEF (t=8.467, P<0.1) was significantly higher than in the control group. The SDNN, rMSSD, p50NN, LF, HF and TP in the diabetic group were significantly lower than in the control group (all P<0.1). Multivariate Logistic regression analysis showed that LATEF was independently correlated with HbA1c (OR=0.2,5%CI:0.239～0.633, P=0.7), LVMI (OR=0.0,5%CI:0.195～0.608, P=0.3) and 24h LF (OR=0.7,5%CI:1.486～3.812, P<0.1). GLS was independently correlated with HbA1c (OR=0.7,5%CI:0.380～0.782, P=0.023), LVMI (OR=0.2,5%CI:0.971～0.999, P=0.3), E/e′(OR=0.4,5%CI:0.255～0.486, P=0.039) and 24h LF (OR=6.1,5%CI:4.330～10.097, P<0.1). Conclusions LA phase function and autonomic function are significantly impaired in asymptomatic diabetic patients. The LA storage function, catheter function, and auxiliary pump function as assessed by volume and strain methods are significantly affected by diabetes. These findings may partially explain the increased cardiovascular morbidity and mortality in atrial fibrillation in diabetic patients.

Abstract:Aim To explore the correlation between brachial-ankle pulse wave velocity (BaPWV) and early renal damage in young and middle-aged patients with essential hypertension and its diagnostic value. Methods A retrospective study was conducted on 317 young and middle-aged patients with essential hypertension. The glomerular filtration rate (eGFR) was estimated by the chronic kidney disease epidemic cooperation equation (CKD-EPI). Hypertensive patients were divided into two groups:111 patients with abnormal renal function (eGFR<90 mL/(min·1.73 m²)) and 206 patients with normal renal function (eGFR＞90 mL/(min·1.73 m²)). The BaPWV, blood lipid combination, serum creatinine, urea nitrogen, fasting blood glucose, urinary microalbumin, cystatin C and homocysteine were detected and compared between the two groups. The eGFR <90 mL/(min·1.73 m²) was used as the criterion to diagnose early renal damage. The sensitivity and specificity of BaPWV in diagnosing early renal damage in young and middle-aged patients with essential hypertension were evaluated by ROC curve. Results ①The BaPWV, systolic blood pressure, serum creatinine, urea nitrogen, cystatin C and homocysteine in patients with abnormal renal function were higher than those in patients with normal renal function (P＜0.05). ②Pearson correlation analysis showed that BaPWV was negatively correlated with eGFR in young and middle-aged patients with essential hypertension (r=－0.339, P＜0.05). After adjusting for homocysteine, urinary microalbumin, systolic blood pressure, diastolic blood pressure and cystatin C, BaPWV was still an independent risk factor for early renal damage in patients with essential hypertension (OR=0.8,5%CI:0.997～0.999, P<0.05). ③ROC curve showed that the area under the curve of BaPWV was 0.676 (95%CI:0.616～0.736).When BaPWV was taken 1 479.5 cm/s, the diagnostic efficiency was the highest, the sensitivity was 76.7%, and the specificity was 56.3%. Conclusions BaPWV is associated with early renal impairment in young and middle-aged patients with essential hypertension, and BaPWV has certain significance in the diagnosis of early renal impairment in young and middle-aged patients with essential hypertension. BaPWV>1 479.5 cm/s can be used as a sensitive index in the diagnosis of early renal impairment in young and middle-aged patients with essential hypertension.

Abstract:Aim To explore the risk factors of atherosclerosis (As) in young and middle-aged premenopausal women by detecting the biochemical indicators and other exposure factors of young and middle-aged premenopausal women.Methods Young women (≤50 years old) who underwent physical examination in the Affiliated Hospital of Taishan Medical University from January 2013 to March 2016 were involved into this study. 390 young premenopausal women were enrolled, aged 26-50 years old, with an average of (45.6±4.4) years old. Carotid arteries of all the cases were assessed using PHILIPS iE 33 color Doppler echocardiography system with the liner probe of 7.5-10 MHz frequency. The arterial intima-media thickness and plaque were measured and recorded. According to the echo results, the cases were divided into 2 groups:As group (n＝191) and Control group (n＝199). Detailed inquiries were made on the past medical history and family genetic history of all the selected subjects, and blood pressure, height and body mass were measured. The indexes of blood lipid, fasting blood sugar, glycosylated hemoglobin, inorganic ions, liver function, kidney function, thyroid function, blood cell analysis and urine analysis were determined by automatic biochemical analyzer. Results The differences of age, grade 3 hypertension, diabetes history, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease, low density lipoprotein cholesterol, total cholesterol, apolipoprotein B, β2 microglobulin, fasting blood sugar, glycosylated hemoglobin, urinary glucose, bicarbonate, chloride ion were statistically significant between the As group and the control group (P＜0.05). Univariate Logistic regression analysis showed that the incidence of As in young, middle-aged and premenopausal women was positively correlated with age, grade 3 hypertension, diabetes history, long-term drinking history, smoking history (including passive smoking), family history of early coronary heart disease, low density lipoprotein cholesterol, total cholesterol, apolipoprotein B, β2 microglobulin, fasting blood glucose, glycosylated hemoglobin, urinary glucose, blood bicarbonate, etc. Further multivariate Logistic regression analysis showed that age, grade 3 hypertension, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease and elevated low density lipoprotein cholesterol were independent risk factors for As in young and middle-aged women. Conclusion Age, grade 3 hypertension, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease and elevated low density lipoprotein cholesterol are independent risk factors for As in young and middle-aged premenopausal women.

Abstract:Aim To investigate the efficacy and safety of dabigatan ester in antithrombotic therapy in coronary heart disease patients with percutaneous coronary intervention (PCI) combined with atrial fibrillation and high bleeding risk. Methods A total of 140 coronary heart disease patients with PCI combined with atrial fibrillation and high bleeding risk who had been admitted to the Second Affiliated Hospital of Shenyang Medical College from May 2016 to October 2018 were enrolled. The patients were randomly divided into the dabigatan ester group and the control group. Both groups of patients were treated with triple antithrombotic drugs from the beginning of PCI to 4 weeks after surgery, and then changed to double antithrombotic drugs until 12 months after surgery, in which the dabigatan ester group was given dabigatan ester and the control group was given warfarin. The platelet count, coagulation function, liver function and rental function were compared between the two groups of patients before and after PCI. The bleeding and thromboembolic events were observed simultaneously. Results There were no significant differences in platelet count, plasma D-dimer, fibrinogen (FIB), liver function, and renal function between the two groups before and after treatment (P>0.05). Activated partial thromboplastin time (APTT) was increased after treatment in both groups. Compared with the control group, the increase of APTT after treatment was more significant in the dabigatan ester group and the difference was statistically significant(P<0.05). International normalized ratio (INR) was increased in both groups after treatment. Compared with the dabigatan ester group, the increase of INR after treatment in the control group was more significantly obvious (P<0.05), and the level of INR remained at the standard level(2.0～3.0). The incidence of bleeding events and thromboembolic events in the dabigatan ester group was significantly lower than that in the control group (P<0.05). Conclusion During the antithrombotic therapy for coronary heart disease patients with PCI combined with atrial fibrillation and high bleeding risk, antiplatelet drugs combined with dabigatan ester, compared with warfarin, can more effectively prevent thromboembolism events, and significantly reduce the incidence of hemorrhage events.

Abstract:Aim To investigate the associations of body mass index(BMI), waist circumference(WC), and neck circumference(NC) with hypertension in elderly men and women. Methods The study performed a cross-sectional survey by cluster sampling among the elderly of 65 years or older in 11 residential committees of Puxing Community, Pudong New District, Shanghai. The Excel software was used to construct a database, and the SPSS statistical software(Version 17.0) for univariate and multivariate analysis. It also performed analysis on blood pressure across the quartile distributions of neck circumference in women. Results A total of 2 092 subjects included 971 men(46.4%) and 1 121 women(53.6%). BMI, waist circumference and neck circumference were higher in hypertensive subjects than normotensive subjects both men and women(P<0.1). The proportions of general obesity, abdominal obesity and greater neck circumference were significantly higher in hypertensive subjects than in normotensive subjects(P<0.1). In multivariate Logistic regression analysis with adjustment for other covariables, all three obesity indices were associated with hypertension. With mutually adjustment for other obesity indices, only greater neck circumference was significantly associated with hypertension in elderly women(OR 1.4,5%CI 1.03～2.01, P=0.032) for additional adjustment with BMI, and(OR 1.6,5%CI 1.12～2.18, P=0.9) for additional adjustment with waist circumference. The level of systolic and diastolic blood pressures and the prevalence of hypertension increased with the quartile distributions of neck circumference in elderly women. The risk of hypertension was significantly higher in those with the neck circumference ≥36 cm compared with those whose neck circumference <32.5 cm(OR 2.1,5%CI 1.51～3.24, P< 0.1). ConclusionsIn this elderly population, all three obesity indices was associated with hypertension. The neck circumference was associated with hypertension independently of other two obesity indices in elderly women.

Abstract:Phytosterols have many functions such as lipid-lowering, anti-inflammatory and anti-oxidation, and play a significant role in preventing atherosclerosis and treating cardiovascular diseases. This article analyzes a number of experimental research to review the function and mechanism of phytosterols, and the latest research progress on the relationship between plant sterols and cardiovascular diseases.

Abstract:Macrophages play central roles in the initiation, growth, and ultimately rupture of atherosclerotic plaques. Altered metabolism is the key feature that dictates macrophage function and subsequent disease progression. This review explores how the core factors of plaque microenvironment shape the metabolic rewiring of macrophages in atherosclerosis as well as how these metabolic shifts in turn alter the immune-effector and tissue-reparative functions of macrophage. Finally, this review offers insight into the challenges and opportunities of using immune metabolism to modulate macrophage responses in disease.

Abstract:The high incidence, high disability rate and high mortality of atherosclerotic related stroke have a serious effect on the society, patients and their families. Therefore, timely and effective diagnosis is particularly important for clinicians to accurately evaluate the risk factors of the disease and select effective treatment methods. Research shows that the expression changes of more and more protein, microRNA and lipid factors are closely related to the occurrence, development and prognosis of atherosclerotic related stroke, which may be potential biomarkers of stroke. In this paper, the biomarkers of atherosclerotic related stroke were reviewed systematically by consulting the domestic and foreign literature, in order to provide new ideas for the prevention and treatment of atherosclerotic related stroke.

Abstract:Saikosaponins are the main active ingredients of Bupleurum chinense, including five subtypes:protoglycoside, homoannular diene, heteroannular diene, oleanolic acid and △¹² oleanane. Saikosaponins have strong anti-inflammatory activities. In vivo studies have shown that saikosaponins can effectively alleviate inflammatory diseases and reduce the expression of pro-inflammatory cytokines, mainly by inhibiting the nuclear factor-κB signaling pathway. Saikosaponins have antioxidant activities. It can significantly reduce the levels of reactive oxygen species and malondialdehyde which is one of the lipid peroxidation products, and enhance the activities of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Saikosaponins may also have lipid-lowering effects. Based on the roles of saikosaponins in anti-inflammation, anti-oxidation and lipid-lowering effects, saikosaponins are expected to be used in the prevention and treatment of atherosclerosis.