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Objective To study the molecular mechanism of atherosclerosis induced by intravascular pressure.Methods Technic aortic coarctation (TAC) was performed in ApoE-/-mice (n＝8) and control littermate (n＝8) mice.HE staining was performed in the vessels upstream and downstream of the mice models.In vitro,hypoxia inducible factor-1a (HIF-1α),heme oxygenase,reactive oxygen species and phosphorylated AMP activated protein kinase (AMPK) were analyzed in different intravascular pressure with a myograph system that allowed independent variation of flow and pressure.Results After one month of TAC,ApoE/ mice in a normal chow diet developed occlusive plaque and accelerated atherosclerotic lesions exclusively in upstream high-pressure vessel segments.In vitro,HIF-1α was increased,heme oxygenase was higher over(2.7 ±0.6) fold,reactive oxygen species and phosphorylated AMPK were also enhanced in high intravascular pressure perfused vessel segments as compared with low intravascular pressure perfused vessel segments (all P＜0.05).Conclusions Intravascular pressure elevation can activate hypoxia and metabolism-associated pathways in the arterial wall,and predispose atherosclerosis accelerated.
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Objective To evaluate the expression of epidermal growth factor-like domain 7 (Egfl7) in atherosclerotic plaques and effects of its small interference RNA (siRNA) on angiogenesis gene expression in human endothelial cell line (HUVEC). MethodsEgfl7 expression in atheroscleroticplaquesweredetectedinhumaniliacarteryandmousearteriaeusing immunohistochemistry and immunofluorescence stainings.The siRNA targeting Egfl7 was transfected into HUVEC by lipofectamine with non-transfected cells and unconcerned siRNA as controls.At 0 h,12 h,24 h and 48 h after intervention,the levels of mRNA and protein of Egf17,vascular endothelial growth factor(VEGF),platelet derived growth factor-A (PDGF-A),platelet derived growth factor-B (PDGF-B),vascular cell adhesion molecule(VCAM) and intercellular adhesion molecule (ICAM)were measured by RT-PCR and Western blotting,respectively. ResultsThe expressions of Egfl7 in human iliac artery and mouse arteriae were increased.The expressions of Egfl7 in HUVEC at the levels of mRNA were[(0.14±0.02),(0.09±0.01),(0.02±0.01)]and the levels of protein[(0.71±0.11),(0.39±0.09),(0.07±0.01)]at 12 h,24 h and 48 h after siRNA intervention,respectively,which were decreased as compared with 0 h intervention [(0.31 ±0.05) and (0.93±0.08) ].Other genes such as VEGF,PDGF-A and PDGF-B were reduced or silenced at the levels of protein and mRNA in HUVEC with siRNA longer interventions(all P＜0.05).ConclusionsThe expression of Egfl7 in atherosclerotic plaques is increased.The siRNA inhibiting Egfl7 gene expression results in silence of other factors involved in angiogenesis.
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Objective To investigate the relationship between the expressions of angiotensin converting enzyme 2(ACE2)/ACE mRNA in myocardium-nephors and the blood pressure in spontaneously hypertensive rats (SHR).Method A total of 18 male of 12 weeks old SHRs and 18 male of 12 weeks old Wistar Kyoto(WKY)rats were got for the experimental study.Nine SHRs and 9 WKY rats were randomly taken out as controls and sacrificed for detecting the mRNA expressions and protein of ACE2 and ACE.Other halves of rats of both groups were fed for 12 weeks and then sacrificed for detecting of the same biomarkers as in controls.The mRNA expressions of ACE2 and ACE were determined by real-time quantitative RT-PCR.The protein level of ACE2 and ACE were determined by immunohistochemistry.Results Systolic blood pressure(SBP)in SHRs of 12 and 24 weeks old increased compared with that in WKY(all P＜0.01).SBP in SHRs of 24 weeks old increased compared with that in SHRs of 12 weeks old(P＜0.01).The cardiac and renal expressions of ACE2 mRNA in SHRs of 12 and 24 weeks old were all significantly lower than those in WKY rats(P＜0.01).The expressions of ACE mRNA in SHRs of 12 and 24 weeks old were all significantly higher than those in WKY rats(P＜0.05,P＜0.01).The cardiac and renal expression of ACE2 mRNA in SHRs of 24 weeks old was significantly lower than that in SHRs of 12 weeks(P＜0.01).The myocardial and renal expression of ACE mRNA in SHRs of 24 weeks old was significantly higher than that in 12 SHRs of weeks old(P＜0.01).The positive reactions of ACE2 protein found in kidney displayed in brown colur.The ACE2 proetin appeared in uniform distribution of brown granules in WKY rats and comparatively scanty distribution of brown granule in SHRs.Conclusions There are correaltions between the expressions of ACE2/ACE mKNA as well as protein and blood pressure.
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Objective To explore the relationship of plasma level of B-type natriuretic peptide (BNP) with cardiovascular risk,the severity of coronary heart disease(CHD),and the short-term prognosis in patients with type 2 diabetes. Methods 154 patients with type 2 diabetes,of them 95 cases complicated with CHD and 65 with hyper-tension were selected in this study. The CHD patients were diveded into 3 groups: AMI(n=32), UAP(n=33) and SAP(n=30). The relationship of the plasma BNP levels with cardiovascular risks, with each coronary heart disea-ses,were observed. The patients were followed up for 6 months to study the predicting role of BNP on the death in pa-tients accompanied with CHD. Results The plasma BNP level was (397.34±217.79) ng/L, which was correlated with age, CRP, hypertension and CHD (r=0.631,0.672, 0.762,0.857, P<0.05 for each);the plasma BNP levels increased with age(r=0.896,P<0.01):(57.6±12.3) ng/L in patients <50 years old,(146.2±53.4)ng/L in patients 50≤and < 59 years old, (388.4±67.5) ng/in patients 60≤and < 69 years old, and (423.8±132.6) ng/L in patients≥70 years old (P<0.01 or P<0.05). The plasma BNP levels, was higher in patients with hyper-tension than that in patients without hypertension [(314.7±125.3) ng/L vs (136.8±98.7) ng/L, P<0.01];Higher in patients with CHD than that in patients without CHD [(425.03±200.80)ng/L vs (37.64±21.57) ng/L,P<0.01)]. The short-term prognosis of patients with CHD was correlated with the levels of BNP, and BNP levels≥485 ng/L may be an independent predicting factor for cardiac death within one month. Conclusions Plas-ma levels of BNP were associated with some cardiovascular risks,which may be one of biomarkers for cardiovascular risks in patient complicated with CHD.
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Objective To investigate relationship between atrial septal thickness and atrial function by transesophageal echocardiography(TEE). Methods TEE and automatic bound detection (ABD) were performed in 83 consecutive sinus rhythm subjects including four groups: control group, nonrheumatic heart disease group, rheumatic mild mitral stenosis group and rheumatic severe mitral stenosis group. Results Atrial septal thickness(AST)and atrial septal thickness fraction (ASTF) were different in various heart diseases. There was high correlation respectively between left atrial diameter(LAD) and AST(r= -0.601 8 ,P
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Objective To investigate the independent echocardiographic pathogenesis associated with left atrial spontaneous echo contrast(SEC) formation in patients with atrial fibrillation(AF).Methods Twenty-one patients with valvular AF and twenty-three patients with nonvalvular AF undergoing transthoracic and transesophageal echocardiography(TTE/TEE) were studied.Morphological and functional parameters of the heart in patients with AF were detected by TTE,while the sizes of the left atrial appendage(LAA),its Doppler flow patterns,Doppler flow patterns of the left upper pulmonary vein and integrated backscatter(IBS) values of left atrial SEC relative to those of the left ventricle were measured by TEE.Results There were the following 10 variables significantly associated with the left atrial SEC,some of which associated positively with SEC were left atrial diameter(r=(0.40252),P=(0.0061)),diameter of the open mouth of LAA to the left atrium(r=(0.37816),P=(0.0161)),while the others of which associated negatively with SEC were antegrade/retrograde blood flow velocity peak,integrate(RVi) and retrograde blood flow velocity mean(RVm) values,and S/D wave peak,S wave integrate(Is) and D wave mean(Md) values,their r values ranged from(-0.40379) to(-0.32832),their P values between(0.0018) and(0.0386).Collinearity analyses suggested that RVi,RVm,Is,Md represented completely all the blood flow velocity parameters of LAA and the left upper pulmonary vein,respectively.Multivariate analyses demonstrated that RVm and Md were the independent predictors of the left atrial SEC in patients with AF(both P
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AIM: To elucidate the relationship between the intracellular calcium concentration changes and left ventricular hypertrophy and function in the spontaneously hypertensive rats (SHR). METHODS: Intracellular free calcium concentrations were measured by Fura 2 methodology and left ventricular function quantitated by cardiac catheterization in 20 SHR aged 10, 22, and 34 weeks and 20 age-matched Wistar-kyoto (WKY) rats. RESULTS: (1) The systolic blood pressure(SBP), intracellular calcium concentrations and left ventricular mass / body weight index ( LVM/BW) were significantly higher in all three age groups of SHR than the corresponding groups of WKY; (2) Compared with age-matched WKY groups, the peak left ventricular pressure descending rate(-d p /d t max ) decreased while left ventricular relaxation time constant (?)increased significantly in SHR aged 22 and 34 weeks. The peak left ventricular pressure ascending rate(d p /d t max ) and the left ventricular contractility index were significantly increased only in the 34 weeks SHR; (3) Intracellular calcium concentrations showed a positive correlation with LVM/BW,SBP,-d p /d t max and ?( r =0 47-0 83, P
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AIM: To establish the experimental acute pulmonary embolism(APE) model and observe the left and right ventricular pressure-volume relationship in different overload situations. METHODS: The present study consisted of seven anesthetized mongrel dogs that were divided into the control group, moderate APE group and severe APE group according to the various phase and different pressure load during the experiment. APE model was induced by suture piece injection through right cardiac catheterization. The hemodynamic indexes were measured by the simultaneous cardiac catheterization and echocardiography.RESULTS: (1) In the group with moderate APE, the pressure-volume relationship of right ventricle tended to right-upward shift, the area of chart increased, the shape of chart transformed form triangle to rectangle. The mild parallel leftward shift, the area of chart decreased mildly and no change of chart shape was observed in the pressure-volume relationship of left ventricle. (2) In the group with severe APE, the chart of right ventricular pressure-volume relationship tended to right-upward shift continuously, the area of chart decreased. The chart of the left ventricle tended to left-downward shift and no change of chart shape was observed in the pressure-volume relationship of left ventricle, the area of chart decreased. The erose shape of charts was also found.CONCLUSION: The chart of ventricular pressure-volume relationships is a practical and reliable method to evaluate left and right ventricular hemodynamic in APE.