Abstract:Aim To observe the expression of cathepsin L(Cat L) in atherosclerotic lesion and investigate its role in lipid accumulation of macrophage. Methods Atherosclerosis model of rabbit carotid artery was established by using ringer of carotid artery.Immunohistochemisty was taken to examine the expression of Cat L in plaques.RAW264.7 macrophage was cultured and treated with various concentrations of oxidized low density lipoprotein(ox-LDL).The mRNA level,the protein expression and the activity of Cat L were detected by reverse transcription polymerase chain reaction(RT-PCR),Western blot and spectrofluorimeter,respectively.The RAW264.7 macrophage was pretreated with various concentrations of Cat L inhibitor,the accumulation of cellular lipid was detected by oil red O staining and high performance liquid chromatography(HPLC). Results Cat L was highly expressed in atherosclerotic lesion,while very weak positive staining was observed in normal vascular.After treatment with oxidized low density lipoprotein,the Cat L mRNA levels were not obviously different among groups(P>0.05).However,the protein expression and the activity of Cat L were increased with a concentration-dependent manner(P<0.05).With pretreatment of Cat L inhibitor,the deposition of lipid was inhibited responding to the inhibitor concentration. Conclusion Cat L was highly expressed in the atherosclerotic plaque and involved in the process of macrophage lipid metabolism.

Abstract:Aim To explore whether oxidative stress mediates doxorubicin-induced cardiotoxicity by inhibiting cystathionine-γ-lyase(CSE) expression and activity. Methods H9c2 cells treated with doxorubicin were used as the model of doxorubicin cardiototoxicity.H9c2 cells were pretreated with N-acetly-L-cysteine(NAC) 60 min prior to treatment with DOX so as to examine the role of oxidative stress in DOX-induced injury.Cell viability was measured by cell counter kit-8.The level of reactive oxygen species(ROS) was tested by dichlorfluorescein staining and photofluorography.Expression of CSE was detected by Western blot assay.Activity of CSE was examined by methylene blue test assay. Results Exposure of H9c2 cells to 5 μmol/L doxorubicin induced significant cardiotoxicity,leading to a decrease in cell viability.Doxorubicin not only enhanced ROS generation,but also inhibited CSE expression and activity in H9c2 cells.Pretreatment with NAC attenuated doxorubicin-induced ROS generation and cardiotoxicity,and also blocked the inhibitory effect of CSE expression and activity by doxorubicin. Conclusion ROS may mediate doxorubicin-induced cardiotoxicity by inhibiting CSE expression and activity.

Abstract:Aim To explore the influence of adipocyte's triglyceride anabolism and visfatin secretion after silence adipocyte fatty acid binding protein(A-FABP) genes by RNA interference. Methods 3T3-L1 preadipocytes were cultured in vitro and were induced to differentiate into adipocytes,then the adipocytes were cultured with concentration from 0 to 1 mmol/L fatty acid,adipocyte's triglyceride production and visfatin secretion were measured.The micro RNA(miRNA) expression vector plasmid about A-FABP genes was constructed and then transfected with the 3T3-L1 mature adipocytes.A-FABP mRNA expression and A-FABP protein expression were measured by reverse transcription polymerase chain reaction(RT-PCR) and Western blot.After and before slience A-FABP,the adipocytes were cultured with concentration of 0.5 mmol/L fatty acid,visfatin mRNA expression in adipocyte were measured by RT-PCR,adipocyte's triglyceride anabolism and visfatin secretion were detected. Results With the concentration of fatty acid risen in adipocytes,the concentration of triglyceride in adipocyte were raised(P<0.05),the concentration of visfatin in adipocyte were raised too(P<0.05).Constructing the miRNA expression vector plasmid about A-FABP genes,then transfecting the 3T3-L1 mature adipocytes,the expression of mRNA and protein about A-FABP genes were obviously restrained(P<0.05).After silence AFABP genes,the concentration of adipocyte's triglyceride was obviously lower than before(P<0.05),the concentration of visfatin secretion was obviously lower than before(P<0.05). Conclusion After silence A-FABP genes by RNA interference,the concentration of adipocyte's triglyceride anabolism and visfatin secretion were lower than before.

Abstract:Aim To study the non-lipid mechanisms of atorvastatin treating atherosclerosis by observing the changes of oxidative stress and inflammatory response. Methods The rabbit model of atherosclerosis were prepared by feeding the high fat diet and immune stimulation,then 0.435 mg/(kg·d) suspension of atorvastatin was given for 1 month.It was observed for the rabbit serum superoxide dismutase(SOD) activity,malondialdehyde(MDA) and oxidized low density lipoprotein(ox-LDL) levels and lectin-like oxidized low density lipoprotein cholesterol receptor-1(LOX-1),vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),monocyte chemoattractant protein-1(MCP-1) gene and protein expression. Results Compared with the control group,rabbit serum SOD activity was significantly decreased(P<0.01),serum MDA,ox-LDL was significantly higher(P<0.01);mRNA and protein expression of aortic LOX-1,VCAM-1,ICAM-1,and MCP-1 were significantly increased(P<0.05 or P<0.01) in atherosclerosis model group.Compared with model group,rabbits serum SOD activity was significantly increased(P<0.01),serum MDA,ox-LDL levels were significantly decreased(P<0.01);mRNA and protein expression of aortic LOX-1,VCAM-1,ICAM-1,and MCP-1 were significantly lower in atorvastatin group(P<0.05 or P<0.01). Conclusions Atorvastatin possesses anti-oxidative stress and inflammatory response,thereby it can protect the vascular endothelium and play a therapeutic role in atherosclerosis.

Abstract:Aim To study the modern biological intention of theory "For those people whose heart is hurt we should mediate the nutrient and the defensive" and the function of Guizhi Tang on improving microcirculation in rat experimental hyperlipemia and myocardial ischemia. Methods The early changes of hyperlipid and atherosclerosis are caused by utilizing multiple factors including feeding hyperlipid,propylthiouracil and high doses of vitamine D3(VD3).Based on the above,the myocardial ischemia model was established by injecting high doses of pituitrin.Measuring the total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDLC) and low density lipoprotein cholesterol(LDLC) in the 6th,12nd and 18th week respectively.Determine blood viscosity(low,middle and high shear rate),plasma viscosity,hematocrit,erythrocyte aggregation index and the index of erythrocyte deformability. Results Guizhi Tang significantly improves the indexes of blood lipid metabolism,increases TC,TG and LDLC,and decreases HDLC.Guizhi Tang can notably decrease blood vicosity,blood deoxidize viscosity,plasma viscosity and relative viscosity,improve hemorheology of red blood cell. Conclusions Guizhi Tang has the marked function of inproving microcirculation.Guizhi Tang can improve myocardial blood supply,decrease the ocurrance and development of main heart and vascular disease.

Abstract:Aim To investigate the effects of rosiglitazone on left ventricular hypertrophy in 5/6 nephrectomized rats. Methods Chronic renal failure of rats was induced by 5/6 nephrectomy.Then the inhibiting development of left ventricular hypertrophy(LVH) mechanism of the rats was explored by observing the nephrectomized rats which were randomly allocated into four groups: XL group(rosiglitazone treatment,5 mg/(kg·d)),DL group(rosiglitazone treatment,15 mg/(kg·d)),model group and sham group,in which the rats with sham operation served as control.5 mg/kg rosiglitazone,15 mg/kg rosiglitazone were respectively delivered daily via gavage for a period of eight weeks.The urinary protein,blood urea nitrogen(BUN),serum creatinine(Scr),blood pressure(BP),angiotensin Ⅱ(AngⅡ),endothelin(ET),body weight(BW),left ventricular weight(LVW) and LVW/BW were measured at the end of the study.Left ventricular hypertrophy was accessed by pathological analysis,and myocardium collagen fibers were stained with Picric acid-Sirius red. Results Compared with model group,the blood pressure of rats in XL group and DL group substantially decreased(P<0.01).So was the case with 24 hours urinary protein,Scr,BUN and plasma AngⅡ,ET.Compared with sham group,the ratio of left ventricle weight to body weight as well as collagen expressions of the left ventricular myocardium in the model group significantly increased(P<0.05).Compared with model group,the above parameters in DL group significantly decreased(P<0.01). Conclusion Rosiglitazone can obviously lower the blood pressure,reduce 24 hours urinary protein,BUN,Scr and recover renal historical damage,regress left ventricular hypertrophy,attenuate remodeling of myocardial collagen network in rats with chronic renal failure.The effect of rosiglitazone is possibly mediated by AngⅡ and ET.

Abstract:Aim To investigate the effect of lycopene in endothelial progenitor cells of human peripheral blood and its underlying molecular mechanism. Motheds The promotion survival effect of lycopene in different concentrations on endothelial progenitor cells was measured by thiazolyl blue(MTT) assay.Cell cycle was analyzed by flow cytometry.The expression levels of cyclin-dependent kinase 4(CDK4) and cyclin D1 were detected by reverse transcription polymerase chain reaction(RT-PCR) and real-time polymerase chain reaction(real-time PCR) and Western blot. Results The MTT assay showed that lycopen promoted survival effect on endothelial progenitor cells in a time and dose-dependent manner.Flow cytometry analysis revealed that G1 phase of endothelial progenitor cells was decreased after exposed to different concentrations of lycopene.The expression levels of CDK4 and cyclin D1 were increased significantly after treated with lycopene in a dose-dependent manner using RT-PCR,real-time PCR and Western blot. ConclusionThe promotion survival effect of lycopene in endothelial progenitor cells is related to G1 phrase reducing through increased expression levels of CDK4 and cyclin D1.

Abstract:Aim To explore the modification of inositol 1,4,5-trisphosphate receptor type Ⅰ(IP3RⅠ) expression by calcineurin in calcification of vascular smooth muscle cells. Methods Rat aortic vascular smooth muscle cells after subculture were randomly divided into control group,calcification group and cyclosporine A(CsA) group.Rat aortic vascular smooth muscle cell calcification model was constructed by NaH2PO4.Expression of IP3RⅠand calcineurin was determined by RT-PCR and Western blot methods.Alkaline phosphatase(ALP) Activity and Ca2+ concentration were determined by colorimetric method.CaN activity was determined by ELISA. Results Expressions of IP3RⅠand CaNB mRNA and protein increased in calcification group compared with control group(P<0.01).Expressions of IP3RⅠand CaNB mRNA and protein decreased in CsA group compared with calcification group(P<0.01).Ca2+ concentration and CaN and ALP activities of rat aortic smooth muscle cells increased in calcification group compared with control group(P<0.01).ALP activity and Ca2+ concentration increased in CsA group compared with calcification group(P<0.05 or P<0.01).CaN activity decreased in CsA group compared with calcification group(P<0.01). Conclusions CaN can enhance the expression of IP3RⅠmRNA and protein in cell calcification.

Abstract:Aim To observe the effect of tanshinone ⅡA on asymmetry dimethyl arginine and NO in aortic endothelial cells of diabetic rats. Methods The diabetic model rats was induced and its aortic endothelial cells were primary cultured by tissue patch and intervened with 0,25,50 mg/L Tanshinone ⅡA sulfonate for 6 h,12 h and 24 h.The contents of asymmetry dimethyl arginine and NO in cell culture were determined by ELISA method and nitrate reductase method,respectively. Results The inhibiting effect of Tanshinone ⅡA sulfonate on asymmetry dimethyl arginine was in a dose-and time-dependent manner.The difference between each group had statistical significance(P<0.05).The promoting effect of secretion of NO was parallel to the increase of concentration,and it reached the peak in 12 h(P<0.05).Conclusion Tanshinone ⅡA can decrease the secretion of asymmetry dimethyl arginine in aortic endothelial cells and promote the synthesis of NO.

Abstract:Aim To investigate association of heart function with renal function in patients with atherosclerotic renal artery stenosis(ARAS)<70%. Methods Renal artery stenosis were <70% in 37 patiens with ARAS,they were divided into two groups based on endogenous creatinine clearance rate(CCr).CCr was detected by serum creatinine(SCr).Group A: 60 mL/min≤CCr<90 mL/min.GroupB: 30 mL/min≤CCr<60 mL/min.Left atrial diameter(LAD),left ventricular end-diastolic diameter(LVDd),interventricular septal thickness(IVST),left ventricular posterior wall thickness(IVPW),early and late wave of mitral valve flow(E/A),ejection fraction(EF),the inside diameter shortened fraction(FS) were determined using echocardiography. Results Compared with group A,indexes of cardia diastolic function and systolic function such as left ventricular ejection fraction(LVEF),EF,FS in group B were significantly decreased(P<0.05).Pearson correlation analysis indicated that CCr was positively correlated to the LVEF(r=0.324,P<0.05)and E/A(r =0.587,P<0.01). Conclusion Severity of diastolic dysfunction and systolic dysfunction correlate with the severity of renal dysfunction in ARAS patients.Renal dysfunction has a high clinical prediction in severity cardiovascular events in ARAS patients.

Abstract:Aim To explore the effect of peroxisome proliferator activated receptors-α/γ(PPAR-α/γ) agonist intervention alone or in combination on serum concentration of high sensitive C-reactive protein(hs-CRP) and matrix metalloproteinase-9(MMP-9) in patients with metabolic syndrome. Methods 256 patients with metabolic syndrom were randomly assigned into basic treatment group,fenofibrate group,pioglitazone group,and fenofibrate+pioglitazone group.All patients received lifestyle interventions and medications to control blood pressure.Additionally,patients in the B group received placebo.Patients in the fenofibrate group received fenofibrate 0.2 g once a day at night.Patients in the pioglitazone group received pioglitazone 15 mg once a day.Patients in the fenofibrate+pioglitazone group received both fenofibrate and pioglitazone as described above.The intervention lasted for 24 weeks.All patients' serum concentration of hs-CRP and MMP-9 were checked pre and post intervention. Results Patients' serum concentration of hs-CRP pre and post intervention in each group were 6.32±1.65 mg/L and 3.52±1.98 mg/L in the fenofibrate group,5.85±1.59 mg/L and 3.33±1.16 mg/L in the pioglitazone group,and 6.49±1.34 mg/L and 2.47±0.91 mg/L in the fenofibrate +pioglitazone group respectively.Patients' serum concentration of MMP-9 pre and post intervention in each group were 179.3±54.9 μg/L and 144.9±30.8 μg/L in the fenofibrate group,188.7±62.4 μg/L and 146.9±27.8 μg/L in the pioglitazone group,and 177.5±58.7 μg/L and 128.8±34.8 μg/L in the fenofibrate+pioglitazone group respectively.Conclusions Fenofibrate or pioglitazone intervention alone can reduce serum concentration of hs-CRP and MMP-9 in patients with metabolic syndrome.A combined use of fenofibrate and pioglitazone was more effective than single intervention with fenofibrate or pioglitazone.

Abstract:Aim To investigate the relationship between atrial fibrillation(AF) and atherosclerosis in patients with hypertension. Methods 145 subjects were enrolled in the present study,according to the results of electrocardiogram,and were divided into two groups: 75 subjects with sinus rhythm and 70 subjects with AF.The baseline clinical characteristics of the patients were analyzed and the intima-media thickness(IMT) and the prevalence atherosclerosis plaques of the carotid artery were measured by echocardiography. Results Individuals with AF had higher carotid artery IMT(P<0.05)and the increased prevalence atherosclerosis plaques(P<0.01) than those with sinus rhythm(P<0.05).Age,the presence of AF,the course of hypertension,and hs-CRP were found to be significantly correlated with carotid artery IMT and the prevalence atherosclerosis plaques.Multivariate logistic regression revealed that AF was independently associated with the presence of carotid prevalence atherosclerosis plaques(OR=1.752,P<0.01) after adjusting for other confounded factors. Conclusions The presence of atrial fibrillation was significantly correlated with carotid artery IMT and the prevalence atherosclerosis plaques after adjusting for age,the course of hypertension,and hs-CRP in patients with hypertension.

Abstract:Aim To investigate the reason of left ventricular(LV) remodeling after successful percutaneous coronary intervention(PCI) in patients with acute myocardial infarction(AMI). Methods Based on the results that whether or not the LV end-diastolic volume index(EDVI) increased 20% from baseline value one year after PCI,233 patients were divided into LV remodeling group(52 cases) and control group(181 cases).The logistic regression analysis was performed to identify independent predictors of LV remodeling after PCI. Results Among all the 233 patients,22.3% had LV remodeling within 1 year after PCI.Compared with the control group,age,creatine kinase-MB(CK-MB) activity,pain to balloon time and the incidences of anterior wall infarction,multivessel disease,prevalence of diabetes and incomplete ST-segment resolution(STR) were higher(P<0.05 or P<0.01),and plasma brain natriuretic peptide(BNP) was higher in LV remodeling group before and 7 days after PCI(P<0.05 or P<0.01) in LV remodeling group.LV remodeling was found to be independently related to CK-MB activity,prevalence of diabetes,incomplete STR,and increasing of BNP at 7 days after PCI. Conclusions CK-MB activity,prevalence of diabetes,incomplete STR,BNP at 7 days after PCI were independent risk factors for LV remodeling in patients with AMI.

Abstract:Aim To study the distribution of serum Cystatin C and analyze its associated influence factors in patients with coronary heart disease. Methods 384 patients with coronary heart disease who underwent coronary angiography were selected in the study.The concentration of serum Cystatin C was measured by immunoturbidimetry.From the pathogenetic condition of coronary heart disease,the number of diseased vessels,we study the distribution of serum Cystatin C and the impact of their risk factors in patients with coronary heart disease. Results With increase of serum levels of Cystatin C,the pathogenetic condition in patients with coronary heart disease became more serious,the number of diseased vessels increased.Likewise,with the increase of the age,levels of serum Cystatin C in patients had the same trend.Sex,hypertension,diabetes,dyslipidemia,smoking history,family history of coronary heart disease such as these risk factors were not correlated with levels of serum Cystatin C.Multivariate analysis demonstrates that age is the main factor which influences level of serum Cystatin C in patients with coronary heart disease. Conclusions Levels of serum Cystatin C is mainly affected by age and other factors,reflects the pathological changes of coronary artery and may be related to the pathogenetic condition of coronary heart disease.Therefore,it is an important factor that can not be ignored in clinical therapy of coronary heart disease.

Abstract:Aim To investigate the efficacy and prognosis of early intervention treatment in cerebral aneurysms ruptured. Methods 101 cerebral aneurysms ruptured patients were selected from April 2007 to February 2011 in our hospital,all patients were treated with interventional micro-coil embolization,including 51 patients with intervene treatment in the early rupture(3 day) as early treatment group,50 patients with non-early interventional treatment as control group.All patients were postoperatively followed-up,with improved mRS score to evaluate the healing effect. Results The healing effect of patients in early treatment group had the significant difference compared with control group(P<0.05),contrast between groups showed that early treatment group's mRS score were significantly lower than that of control group(P<0.05).And contrast within the group showed that mRS score of patients under Hunt-Hess grade Ⅳ was significantly lower than the Hunt-Hess grade Ⅳ,Ⅴ patients(P<0.05).Contrast between the age showed age ≥ 60 patient's mRS score were higher than age <60 patients(P<0.05).Contrast between the aneurysm size and the treatment effect showed small and medium patient's mRS score had significant difference compared with large and huge patients(P<0.05).Early treatment group's complication were significantly lower than that in control group(P<0.05). Conclusion Early intervention micro coil embolization in intracranial aneurysm rupture has the remarkable curative effect,and can significantly reduce the incidence of postoperative complications and the chance of aneurysm rupture again,and improve the patients' outcomes.

Abstract:Aim To investigate the correlativity of carotid artery elasticity and coronary arterial stenosis. Methods 100 subjects who underwent coronary angiography(CAG) were subject to a contemporary examination of ET examination(<15 days).According to the results of CAG,the subjects were divided into four groups,normal,single-branch lesion,two-branch lesion(including left aim branch) and multi-branch lesion.The parameters of carotid elasticity,stiffness parameter β(β),pressure strain elastic modulus(Ep),arterial compliance(AC),were measured by ET technique,and the correlativity of carotid artery elasticity and coronary arterial stenosis was studied. Results The parameters of the carotid elasticity,β,Ep and AC,changed with the development of the coronary heart disease(CHD).Compared with normal subjects,elasticity of the carotid arteries was even worse in CHD patients,especially in multi-branch lesion group.There was no statistical difference in carotid elasticity among normal group,one-branch lesion group and two-branch lesion group.The carotid elasticity decreased more in multi-vessel lesion group than other groups. Conclusions There is a close correlation between carotid elasticity and coronary stenosis.The parameters of carotid elasticity measured by ET(β,Ep and AC) can be used to predict the degree of the coronary stenosis,suggesting their potential roles in distinguishing different risk levels for CHD.

Abstract:Aim Association between the-1562C>T single nueleotide polymorphisms of matrix metalloprotein-9 gene and the occurrence coronary artery disease in Chinese Han population was studied. Methods Case-control studies published before 31 Dec.2010 about the association of matrix metalloprotein-9 gene-1562C>T polymorphism and coronary artery disease in Chinese Han population were searched,all the literatures were evaluated and abstracted based on the defined selection criteria by two independent investigators.Publication bias was tested by funnel plot and the odd ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies.The software Review Manager(version 5.0) and Stata(version 10.0) were used for meta-analysis. Results Seven studies were analyzed,there was no publication bias in 7 reviewed studies.The summarized odds ratios of TT and CT genotype combination versus CC genotype across all 7 studies was OR= 1.47(95% CI was 1.20~1.78,P=0.0001);T genotype versus C genotype was OR=1.41(95% CI was 1.17~1.69,P=0.0002);CC genotype versus TT and CT genotype combination was OR= 0.68(95% CI was 0.55~0.82,P<0.0001);CT genotype versus CC and TT genotype combination was OR=1.45(95% CI was 1.19~1.77,P=0.0002). Conclusions In Chinese Han population,-1562C>T polymorphism in matrix metalloprotein-9 gene is associated with susceptibility of coronary artery disease and T allele might be a risk factor for coronary artery disease.

Abstract:A long-standing association exists between elevated triglyceride levels and coronary heart disease(CHD).However,the extent to which triglycerides directly promote CHD or represent an independent factor of risk has been debated for decades. This paper aims to review the latest advances in the relationship between triglycerides and coronary heart disease from the aspects of pathophysiology and epidemiology,so as to clarify the role triglycerides play in atherogenicity and CHD.

Abstract:With the extension of human life and the increase of the incidence of atherosclerosis,senile degenerative valvular disease(SDVD) are increasingly common,which has become one of the most important reasons of heart failure,arrhythmia,syncope and sudden death in the elderly.SDVD valve is characterized by a large number of calcium deposition,and the most common valvular heart disease in the elderly.The disease usually has a slow progress and a good prognosis.This article mainly focuses on Senile degenerative valve disease of epidemiology,risk factors,pathology,pathogenesis and treatment.