Abstract:Aim To investigate the dynamic changes of adrenomedullin specific receptors components,calcitonin receptor-like receptor(CRLR),receptor activity modifying proteins 2(RAMP2) and RAMP3 mRNA expression in the stress-induced-hypertensive rats.Methods Distribute 48 rats to control group with 18 of them and stress group with 30 of the total randomly.Noise with electric foot shock upon the stress group.Execute all the rats and separate their hypothalamus to isolate the total RNA individually at stress 1,5,10 and 15 d and poststress 5 and 10 d.Determine the changes of the adrenomedullin,CRLR and RAMP mRNA expression of by reverse transcription-polymerase chain reaction(RT-PCR).Results Compared with control group at the same time point,CRLR mRNA expression in hypothalamus upregulated within foot-shock and sound stress 10 d(1.236±0.040 vs 0.941±0.041,p<0.01),then downregulated to a lower level at stress 15 d(0.860±0.041 vs 0.938±0.042,p<0.05);RAMP2 mRNA expression in hypothalamus upregulated to the highest lever at stress 5 d(1.160±0.045 vs 0.897±0.036,p<0.01),then downregulated to a lower lever at stress 15 d and poststress 5 d(0.670±0.021 vs 0.897±0.041,0.719±0.039 vs 0.910±0.032,p<0.01);However RAMP3 mRNA expression upregulated to the highest lever at stress 1 d(1.197±0.053 vs 0.870±0.039,p<0.01),then downregulated to a lower lever at 10,15 d and poststress 5 d(p<0.05 or p<0.01).Even at poststress 10 d,the level of RAMP3 expression still lower than control group at the same time point,but no statistic significance.Conclusion According to the results described above,at the gene level,the expression of ADM specific receptor components CRLR,RAMP2 and RAMP3 mRNA had changed to some degree in the process of chronic stress-induced-hypertension,indicating that ADM specific receptors maybe involve in the stress-induced-hypertension.

Abstract:Aim To investigative nicotinamide adenine dinucleotide phosphate oxidase(NOX4) expression,intracellular reactive oxygen species(ROS) level and cell apoptosis in human umbilical vein endothelial cells(HUVEC) when stimulated with high concentration of glucose.Methods Morphology of HUVEC was observed with inverted microscope,expression of factor Ⅷ related antigen in HUVEC was detected by immunofluorescence.NOX expression in HUVEC was convicted by reverse transcription polymerase chain reaction(RT-PCR) with positive control.Intracellular ROS generation was measured by DCFH-DA,cell apoptosis were measured by PI and Hoechet 33342 staining respectively.Results With high glucose in media,expression of NOX4,intracellular ROS generation and cell apoptosis were all increased.Conclusions High glucose could upregulate NOX4 expression,intracellular ROS production and then lead to cell apotosis.

Abstract:Aim To create an animal model for local change of shear stress to analyze the arterial wall response to different shear stress.Methods A stenosis is modeled by a ring attached to the wall of the left common carotid artery to change flow condition.Numerical simulation of blood flow in the stenosis aorta was performed to obtain the distribution of flow field and wall shear stress.Rabbits were fed normal food,which were sacrificed and arteries were obtained after 4 weeks.The pathological slides were prepared and stained for optical microscopic observation.The content of cholesterol in arteries wall was assayed with High Performance Liquid Chromatography(HPLC).The lipid in plaque was detected with oil red O.Results Blood flow was disturbed significantly at immediate proximal and distal vicinity of stenosis.The shear stress in proximal part of ringer was obviously increased(6 Pa),while the shear stress in distal of ring decreased(0～0.3 Pa).At the end of 4 weeks,rabbits had obviously plaque in proximal part and backend of ringer,while the lesion in proximal part is more severity than distal of ringer.Plaque mainly composed with macrophage derived foam cells at proximal of stenosis,while plaque of distal of stenosis mainly composed with smooth muscle cells.Oil red O shows that there were a great deal of lipid deposited in proximal of stenosis and distal of stenosis.The content of cholesterol in proximal of stenosis(7.6±2.1 mg/g) and distal of stenosis(5.6±1.8 mg/g) was more than control(1.3±0.5 mg/g).Conclusions Shear stress attributed to the neointimal and atherosclerosis,while the high or low shear stress may play different roles to the formation and development of plaque.

Abstract:Aim To explore the relationship between apoptosis in lung tissues and lung ischemia-reperfusion injury,and observe effects of safflower injection on pneumocyte apoptosis in lung ischemia-reperfusion injury.Methods Single lung in situ ischemia reperfusion animal model was used.84 rabbits were randomly divided into control group(C),ischemia/reperfusion 1 h group(IR1h),IR3h,IR5h,safflower injection 1 h group(SI1h),SI3h and SI5h.TdT mediated dUTP nick end labeling(TUNEL),electron microscope,immunocytochemistry and in situ hybridization(ISH) techniques were used to observe apoptosis,pulmonary ultrastructure and Bcl-2,Bax expression respectively in lung tissues of different group rabbits.Results Compared with control group,cell apoptosis,Bcl-2,Bax expression were up-regulated in lung tissues of IR groups(all of p<0.01).The safflower injection susppressed apoptosis as well as expression of Bax,but which improved the expression of Bcl-2 gene and the ratio of Bcl-2/Bax at the same time(p<0.01 or p<0.05,respectively).Electron microscope showed serious pulmonary ultrastructure damage in IR group,but no significant injury was found in SI group.There was a significant positive correlation between AI and Baxprotein,BaxmRNA(r=0.926,0.913;p<0.01,respectively),and there was a significant negative correlation between AI and the ratio of Bcl-2protein/Baxprotein,Bcl-2mRNA/BaxmRNA(r=-0.367,-0.375;p<0.01,respectively).Conclusion Apoptosis participates in lung ischemia reperfusion injury.The protective effects of safflower injection include suppressing the expression of Bax,blocking pneumocyte apoptosis and promoting Bcl-2 expression and the ratio of Bcl-2/Bax in lung ischemia-reperfusion injury.

Abstract:Aim To observe the relationship of p38-mitogen activated protein kinase(p38MAPK) and cardiomyocyte apoptosis in hibernating myocardium(HM).Methods Ten coronary artery disease(CAD) patients scheduled for bypass surgery were underwent preoperative dobutamine stress echocardiography(DSE),doppler tissue image(DTI) to check the position of HM and intraoperative myocardial biopsies.The normal myocardium and the HM were obtained in operation.They were conformed by electron microscope.Cardiomyocyte apoptosis were detected by Tunel,phosphorylation of p38 was detected by Western blot.It was analyzed that phosphorylation of p38 and positive cardiomyocyte nuclei(PCN) of apoptosis of CHM were different or not in hibernating myocardium and normal myocardium.It was analyzed for the relationship of p38MAPK and PCN of apoptosis.Results Phosphorylation of p38 and PCN of apoptosis were significantly increased in CHM compared with normal myocardium.Phosphorylation of p38 and PCN of apoptosis were positive correlation in hibernating myocardium(r=0.816,p<0.05).Conclusion p38MAPK can be triggered by ischemia,and active p38MAPK intervene cardiomyocyte apoptosis.

Abstract:Aim To investigate a potential role of Toll-like receptor 2(TLR2) and platelet factor 4(PF4) in atherosclerosis,We assessed their expression in murine atherosclerotic plaques.Methods Twenty apolipoprotein E-/-mice at the age of 12 weeks were fed by high-fat diet,ten C57BL/6 mice at the age of 8 weeks were fed by standard laboratory chow for 12 weeks,then all of the animal were euthanized.Blood was sampled from the eye,the serum lipids was enzymatically detected.The thoracic and abdominalis aorta was fixed by in situ liquid flow.Thoracic aorta was fix in 10% formalin,paraffin imbedding,serial sections,and HE staining.Aortic lesions of high-fat diet-fed apolipoprotein E-/-mice were examined for TLR2 and PF4 expression by immunohistochemistry.Results Aortic atherosclerotic lesions in all apolipoprotein E-/-mice expressed TLR2,whereas aortic tissue obtained from control C57BL/6J mice showed no TLR2 expression.Serial sections immunostaining showed TLR2 localizing with macrophages and endothelial cells in murine atherosclerotic lesions.Furthermore,PF4 expression in murine atherosclerotic plaques were also observed.Conclusions TLR2 is expressed by macrophages and endothelial cells in murine atherosclerotic lesions,and we find that PF4 is also expressed in the plaques.They may play a role to enhance and sustain the innate immue and inflammatory responses.

Abstract:Aim To further discuss the anti-atherosclerotic mechanism of adiponectin,the impact of adiponectin on cholesterol efflux mediated by ATP binding cassette transporter A1(ABCA1) in THP-1 derived foam cells was studied.Methods THP-1 derived foam cells were incubated with apolipoprotein A1(apoA1),adiponectin,and apoA1+adiponectin in vitro,respectively.RT-PCR,ELISA and HPLC were used to determine the influence of adiponectin on ABCA1 mRNA and protein expression and on intracellular cholesterol content before and after treatments.Results Adiponectin could up-regulate ABCA1 mRNA and protein expression in THP-1 derived foam cells in vitro.Adiponectin alone could enhance the transformation from cholesterol ester to free cholesterol.In combination with apoA1,it could increase the ABCA1 mediated efflux of intracellular cholesterol significantly.Conclusions Adiponectin inhibit intracellular cholesterol deposit in foam cells by enhancing the hydrolysis of intracellular cholesterol ester.It can up-regulate ABCA1 expression,and accelerate ABCA1 mediated intracellular free cholesterol efflux.

Abstract:Aim To investigate the effect of angiotensin Ⅱ(AngⅡ) on cysteine-rich 61(Cyr61) expression and its transduction access in cultured rat vascular smooth muscle cells(VSMC).Methods VSMC were cultured in sticking mass methods.VSMC were treated with AngⅡfor 15 min,30 min,60 min,180 min,which were pretreated with PD98059 for 60 min before AngⅡ treatment.The Cyr61 expression in VSMC were characterized by reverse transcription polymerase chain reaction(RT-PCR) and Western blotting.Results RT-PCR analysis revealed that Cyr61 increased in cells treated with 1 μmol/L AngⅡ for 15,30 min compared with control(p<0.01) and still expressed at 60 min and attenuated at 180 min.Phosphorylated extracellular signal regulated kinase(P-ERK) 1/2 activity increased in cells treated with 1 μmol/L AngⅡ for 30 min compared with control(p<0.01),Cyr61 expression and P-ERK1/2 activity were inhibited by the presence of 20 μmol/L PD98059,a specific inhibitor of ERK1/2.Conclusions AngⅡup-regulates Cyr61 expression in cultured rat VSMC via ERK1/2.This may be a significant mechanism for VSMC proliferation by AngⅡ.

Abstract:Aim To explore the effect and potential mechanism of atorvastatin on C-reactive protein(CRP) secretions in adipocytes from hypercholesterolemic rabbits.Methods Fourteen male New Zealand rabbits(3 months old) were randomly fed with normal diet(n=4),high-cholesterol diet(n=10) for 8 weeks,and then high-cholesterol diet rabbits were assigned to either atorvastatin 1.5 mg/kg·d(n=5) or starch(n=5).Two weeks later,subcutaneous adipose was collected for culture.CRP concentrations in serum and adipocytes culture supernatant were measured by latex particle enhanced immunoturbidometric method.With semi-quantity reverse transcription polymerase chain reaction,peroxisome proliferator-activated receptor(PPAR) γ mRNA expression was determined.Results Serum CRP levels were obviously reduced by two weeks atorvastatin treatment in hypercholesterolemic rabbits.Serum CRP concentrations were correlated with low density lipoprotein cholesterol(LDLC) levels(r=0.890,p<0.001) and CRP secretions from adipocytes(r=0.688,P=0.007).The CRP secretions in adipocytes were intimately associated with LDLC levels(r=0.869,p<0.001) and PPARγ mRNA expressions in adipocytes(r=-0.857,p<0.001).Conclusions Hypercholesterolemia might induce CRP secretions in adipocytes.Atorvastatin reduces CRP serum concentrations and adipocyte secretions in hypercholesterolemic rabbits,which are possibly dependent on its cholesterol-lowering effects and upregulating PPARγ mRNA expressions in adipocytes.

Abstract:Aim Aim To study effect of Tongmai recipe on epidermal growth factor receptor and protooncogene c-myc mRNA expression in aorta of atherosclerotic rabbit.Methods Forty rabbits were randomly divided into four groups:①Control group:10 rabbits were fed with common food twice daily;②Model group:10 rabbits were fed with high cholesterol diet supplemented by cholesterol 0.5 g/(kg·d),yolk 2 g/(kg·d) and lard 2 g/(kg·d);③Low dosage Tongmai recipe administration group(LT group):10 rabbits were fed with high cholesterol diet as well as in model group,simultaneously administrated with Tongmai recipe at a dosage of 7.3 g/(kg·d),④High dosage Tongmai recipe administration group(HT group):10 rabbits were fed with high cholesterol diet as well as in model group,simultaneously administrated with Tongmai recipe at a dosage of 21.9 g/(kg·d).After 16 weeks,epidermal growth factor receptor were assessed by immunohistochemistric assays.c-myc mRNA in aorta were quantified with semiquantitative RT-PCR methodology.Results we found that in model group,accumulation of epidermal growth factor receptors and mRNA expression of protooncogene c-myc in aorta significantly increased as compared to those in control group(0.327±0.030 vs 0.209±0.006,p<0.01;0.52±0.11 vs 0.34±0.07,p<0.01).In HT group,they significantly decreased as compared to those in model group(0.242±0.014 vs 0.327±0.030,p<0.01;0.41±0.07 vs 0.52±0.11,p<0.05).In LT group,there was no significant change as compared to those in model group(0.301±0.027 vs 0.327±0.030 p>0.05;0.44±0.09 vs 0.52±0.11 p>0.05).Conclusion ①Expression of epidermal growth factor receptor and c-myc which promoted proliferation of vascular smooth muscle cells increased in atherosclerotic individuals.②Tongmai recipe may possesses the role of depression of proliferation of vascular smooth muscle cells by depressing the expression of epidermal growth factor receptor and protooncogene c-myc.

Abstract:Aim To ascertain whether N-acetylcysteine(NAC) is helpful for hypertension or not.Methods Male spontaneously hypertension rat(SHR) were randomly divided into three groups:placebo group,NAC group,and base group.Rats in the base group were sacrificed before treatment,and blood samples were detected.Syntolic blood pressure(SBP),nitric oxide(NO),and interleukin-1(IL-1) was measured in placebo group and NAC group.Results The SBP of placebo group was higher than NAC group after treatment.NO was higher in NAC group than placebo group(p<0.05).IL-1 was higher in placebo group than NAC group(p<0.05).Conclusion NAC(10 g/L) can step down blood pressure in spontaneously hypertension rat,and has protective effects on it.

Abstract:Aim To study the distribution of coagulation factor Ⅶ gene polymorphisms in Chinese Han population and the association of the polymorphisms with brain bleeding.Methods Genotypes of coagulation factor Ⅶ were typed in 36 brain bleeding patients and 36 controls by polymerase chain reaction-restriction fragment length polymorphism.Results Coagulation factor Ⅶ allelic frequencies of R,Q were 90.3%,9.7% and 88.9%,11.1% in brain bleeding group and control group respectively.Genotype distribution was in accordance with Hardy-Weinberg equilibrium.There was no significant difference in frequencies of allele and genotype in R353Q polymorphisms between brain bleeding group and control group.Conclusion The R353Q polymorphisms of the coagulation factor Ⅶ gene may not have a relationship with brain bleeding patients of Han Chinese in southern of China.

Abstract:Aim To explore the relation between serum levels of C-reactive protein(CRP) and soluble intercellular adhesion molecule-1(sICAM-1) and Chlamydia pneumoniae(Cpn) infection and coronary heart disease(CHD).Methods Serum levels of CRP,sICAM-1 and IgG,IgM antibodies to Cpn were detected by enzyme-lined immunosorbent assay(ELISA) in 60 patients with CHD and 40 healthy subjects.These patients were divided into four groups:acute myocardial infarction(AMI),unstable angina pectoris(UAP),old myocardial infarction(OMI) and stable angina pectoris(SAP).Results Cpn-IgG positive rates and levels in patients with CHD were significantly elevated compared with control group(p<0.01);Cpn-IgG positive rates between each group weren't different significantly(p>0.05);Cpn-IgG levels in AMI were higher than in OMI,UAP and SAP(p<0.05);Cpn-IgM positive rates in patients with CHD weren't different compared with control group(p>0.05).The levels of CRP and sICAM-1 in patients with CHD were significantly elevated compared with control group(p<0.01);the levels of CRP and sICAM-1 in AMI were significantly higher than in UAP,OMI and SAP(p<0.01);The levels of CRP and sICAM-1 in UAP were higher than in SAP.There was correlation between the levels of CRP,sICAM-1 and Cpn-IgG in patients with CHD(p<0.05).Conclusion The levels of CRP and sICAM-1 may reflect the severity of CHD at some degree.There is correlation between Chlamydia pneumoniae infection and CHD.Both inflammation and infection are revelant to CHD.

Abstract:Aim To explore the relationship between plasma level of B-type natriuretic peptide(BNP) and coronary heart disease(CHD) in patients with type 2 diabetes.Methods 126 patients with type 2 diabetes were selected in this study.31 patients without CHD were as the control;clinical phenotypes of CHD were divided into 3 groups:acute myocardial infarction(AMI) group,32 patients;unstable angina pectoris(UAP) group,33 patients;and stable angina pectoris(SAP) group,30 patients.Plasma levels of BNP were detected on admission in 4 groups.Correlation between BNP and cardiac troponin T(cTnT) which was detected at the same time in SAP,UAP and AMI groups were observed.Results Plasma level of BNP were 41.8±7.5 ng/L,165.2±31.4 ng/L,509.5±125.6 ng/L and 24.1±3.7 ng/L in the patients with SAP,UAP,AMI and the control respectively.The level of BNP was significantly higher in AMI than that in other three groups(p<0.001);the level of BNP was significantly higher in UAP than that in SAP or control(p<0.001).BNP level were highly correlated with cTnT in UAP and AMI(r=0.948,p<0.001).Conclusion Plasma levels of BNP are associated with clinical phenotypes of coronary heart disease and it may reflect degree of myocardial necrosis in patients with type 2 diabetes.

Abstract:Aim To investigate the relationship between plasma concentrations of leptin and the severity of coronary artery stenosis,obesity.Methods According to coronary angiography,73 coronary atherosclerosis(As) patients and 20 healthy controls were enrolled in the present study.The plasma levels of leptin were determined and the relationship between leptin level and Gensini score and body mass index(BMI) was analyzed.Results As the Gensini score increased,the leptin levels increased(p<0.05).The plasma leptin levels in control group,Gensini score 1～30,31～90 and >90 groups were 0.52±0.12 μg/L,0.61±0.15 μg/L,0.77±0.13 μg/L and 0.93±0.13 μg/L,respectively.The plasma concentrations of leptin in As patients were significantly correlated with Gensini score(r=0.643,p<0.01).As the BMI increased,the leptin levels increased(p<0.05).The plasma leptin levels of normal weight,overweight,obesity groups were 0.59±0.17 μg/L,0.75±0.16 μg/L and 0.89±0.11 μg/L,respectively.Conclusions The plasma concentrations of leptin is significantly related to the severity of coronary artery stenosis and obesity.It suggests that leptin may be involved in the development of As.

Abstract:Aim To explore the changes of leptin and soluble leptin receptor(SLR)in patients with chronic heart failure(CHF),the relationship between leptin and NYHA grades and the value of serum leptin in predicating short-term prognosis of patients with CHF.Methods One hundred and twenty patients with CHF and 30 normal controls were included.Serum leptin and insulin was measured by radioimmunoassay(RIMA),SLR by enzyme linked immnuoabsorbent assay(ELISA).Follow up was carried out for 8-12 months.Endpoint events included death and readmission.Kaplan-meirer and COX regression model were employed in prognositc analysis.Results Compared with the control group,CHF group had significantly increased serum leptin and SLR level(12.4±3.0 vs 6.3±2.0 μg/L,p<0.01;42.40±10.0 vs 25.6±10.7 μg/L,p<0.01 respectively).No statistical difference of serum leptin level was found among groups of NYHA grade Ⅱ、Ⅲ and Ⅳ(14.0±1.6 μg/L,12.8±1.0 μg/L,10.8±1.3 μg/L;p>0.05).Kaplan-meier analysis revealed a better survival curve of group with low leptin level than that of group with high leptin level(P=0.044).COX regression model showed that leptin was a significant short-term prognosis predictor(Standard regression coefficient 0.112,p<0.05).Conclusion Patients with CHF have elevated serum levels of leptin and soluble leptin receptor.Serum leptin level is valuable in predicating short-term prognosis of CHF.

Abstract:Aim To investigate the correlation between glycosylated hemoglobin A1c(GHbA1c) and Ⅶ factor activity in type 2 diabetic patients with different types of coronary heart disease(CHD).Methods Concentrations of GHbA1c and plasma activities of Ⅶ were measured in 73 patients with difference types of coronary heart disease and 40 T2 diabetic patients.Results In the patients of actual myocardial infarction and unstable angina pectoris Ⅶ activity was significantly higher than those of diabetic patients(p<0.05).In the old myocardial infarction and stable angina pectoris Ⅶ activity was higher than those of normal controls(p<0.01).There was a positive correlation between the concentration of GHbA1c and activity of Ⅶ in all the patients and controls.Conclusion Concentration of blood glucose positively correlated with Ⅶ factor.Serum blood glucose may play an important role in the pathogenesis of T2 diabetes mellitus by inducing coagulative and fibrinolytic dysfunction.

Abstract:Aim To study the detection rate of coronary artery aneurysm(CAA) in Chinese adults under coronary angiography(CAG),its clinic features and prognosis.Methods Retrospective studies were conducted of the clinical features,treatment and outcome of 8628 patients under CAG.Results Among the 8628 patients,80 had CAA,the total detection rate of was coronary artery aneurysm 0.927%.Among these patients,42 had myocardial infarction,and 72 had narrowing coronary artery(stenosis 50%).Among the 80 cases of CAA,61 arteries had thrombosis.No coronary artery aneurysm had ruptured.Conclusion The detection rate of coronary artery aneurysm in the studied coronary angiography population was 0.927%,coronary artery aneurysm could be responsible for myocardial ischemia and myocardial infarction.

Abstract:Aim To investigate whether the insertion/deletion(I/D) polymorphism in the angiotensin converting enzyme(ACE) gene is associated with essential hypertension in Xinjiang Uyigur isolated population.Methods The study covered 361 hypertension patients and 400 normotensive controls,the variant of ACE I/D was determined by polymorphism chain reaction(PCR).Some biochemical index such as serum total cholesterol(TC),triglyceride(TG),glucose(GLU) and total bilirubin(TBIL) were also measured.Results Using logistic regression analysis,adjusted for age,sex,body mass index(BMI),waist circumference,hip circumference,intake of salt,GLU,TC,TG,there was a relationship between hypertension and ACE gene I/D polymorphism,and the parameter β is 0.246(P=0.0302).The odds ratio for hypertension of DD versus II homozygote individuals was 1.51(P=0.038).Conclusions The results suggest that the I/D polymorphism of ACE gene is associated with the hypertension in the Uyigur population of Xinjiang.And the DD genetype may be the risk factor of hypertension.