Abstract:Aim To investigate the effects of asymmetric dimethylarginine(ADMA)on the expression of macrophage migration inhibitory factor(MIF)in THP-1 monocyte-derived macrophage cells.Methods After induced by 150 nmol/L phorbol 12 myristate 13 acetate(PMA)for 48 h,THP-1 monocyte cells differentiated into macrophage cells.And THP-1 monocyte-derived macrophage cells were identified by immunocytochemistry with anti-human CD68.After THP-1 monocyte-derived macrophage cells were incubated with ADMA of different concentrations(1 μmol/L,5 μmol/L,10 μmol/L,20 μmol/L,30 μmol/L)for 24 h and 20 μmol/L ADMA for 0 h,6 h,12 h,24 h and 48 h,the expressions of MIF in mRNA and protein were measured by means of RT-PCR and enzyme-linked immunosorbent assay respectively.Results Treatments of THP-1 macrophage cells with 5 μmol/L,10 μmol/L,20 μmol/L,30 μmol/L ADMA for 24 h resulted in an increase in the mRNA and protein levels of MIF.Treatments of THP-1 macrophage cells with 20 μmol/L ADMA for 12 h,24 h,48 h,resulted in an increase in the mRNA and protein levels of MIF.Conclusion ADMA upregulated the expression levels of MIF in cultured THP-1 monocyte-derived macrophage cells in a dose-and time-dependent manner,which may result in the atherosclerosis.

Abstract:Aim To investigate the effect of diabetes on rat vascular calcification,and the expression of Msx2 and Wnt3a mRNA in calcified artery of diabetic rat.Methods 48 male Wistar rats were randomly divided into 4 groups:vitamin D3 and nicotine(VDN)group(n=12)undergoing vitamin D3 and nicotine treatment,and diabetes mellitus(DM)group(n=12)undergoing injection of streptozotocin(STZ)to induce diabetes,and diabetes mellitus & vitamin D3 and nicotine(DM+VDN)group(n=12)undergoing injection of STZ and vitamin D3 and nicotine treatment.Another 12 rats were used as normal controls(CON group,n=12).Measurements of metabolic parameters(glucose,insulin,total cholesterol and triglyceride)were performed.von Kossa calcium stain,aortic calcium content and alkaline phosphatase(ALP)activity were used as indicators to determine the extent of vascular calcification.Real-time PCR was performed to detect the expression of Msx2 and Wnt3a mRNA.Results Compared with CON group,four weeks of vitamin D3 and nicotine treatment alone increased the expression of Msx2 and Wnt3a mRNA in aorta slightly(P<0.05),but there were no significant differences in aortic calcium content or ALP activity.In the DM+VDN group,calcium deposition in aorta,aortic calcium content,ALP activity and expression of Msx2 and Wnt3a mRNA in artery increased significantly compared with CON group and VDN group(P<0.05).Conclusion Diabetes may accelerate vascular calcification.Bone-associated transcript factors,Msx2 and Wnt3a are up-regulated in calcified artery of diabetic rat.It suggests that vascular calcification is a process similar to bone formation,and Msx2 and Wnt3a may involve in the occurrence of vascular calcification.

Abstract:Aim To observe the changes of PKGIa mRNA and protein expressive level in cerebral arterial smooth muscle cells(CASMC)induced by bloody cerebrospinal(BCSF)in rats,and to investigate the value of PKGIa signaling pathway in cerebral vasospasm(CVS)after subarachnoid hemorrhage(SAH).Methods The pure CASMC were cultured by tissue-sticking methods.Semi-quantitative reverse transcription and polymerase chain reaction(RT-PCR)were used to examine the PKGIa mRNA expression after CASMC were exposed to BCSF for 24 h and 48h respectively.And PKGIa protein expressions were determined by Western blotting.The changes of CASMC proliferation were determined by MTT and 3H-TdR incorporated way.Results BCSF could stimulate CASMC proliferating.The mRNA and protein of PKGIa could be detected in all groups,and the expressive level of mRNA and protein had a possible relationship with CASMC prolferation.Conclusion The results suggested that PKGIa signaling pathway might play an important role in the CVS after SAH.

Abstract:Aim To investigate the effect of Krüppel-like factor 4(KLF4)overexpression on doxorubicin-induced apoptosis of rat myocardiocytes H9C2.Methods Trypan blue staining and cytometry were applied to detect apoptosis;Western blotting was applied to determine expressions of KLF4 and apoptosis-related gene poly ADP-ribose polymerase(PARP).Results Trypan blue staining and cytometry results showed that doxorubicin could induce apoptosis of H9C2,and the apoptosis rate in KLF4-overexpression group was much higher than that of vector control group,which was 87.90%.Western blotting results showed that doxorubicin treatment could promote KLF4 expression in H9C2 cells,and the expression of PARP fragment was also up-regulated dramatically in KLF4-overexpression group.Conclusion KLF4 could promote doxorubicin-induced apoptosis of H9C2 cells,which potential mechanism may be involved with PARP.

Abstract:Aim Previous study demonstrated that tetramethylpyrazine(TMP)had an inhibitory effect on the TF expression induced by thrombin in human umbilical vein endothelium derived cell line human umbilical vascular endothelial cells(HUVEC).However,its mechanisms were not fully understood.In this study,we observed the role of nitric oxide(NO)and transcription factor NF-κB in the regulation of TMP on tissue factor(TF)expression.Methods HUVEC were cultured in RPMI-1640.TF activity was determined with one-stage clotting assay measuring total cellular pro-coagulant activity(PCA).TF mRNA was examined by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Immunohistochemical analysis was performed to evaluate the translocation of NF-κB.Results NG-nitro-L-arginine methylate(L-NAME)is an inhibitor of nitric oxide synthase(NOS),and it alone had no marked effects on PCA and TF mRNA in HUVEC,but L-NAME significantly decrease the inhibitory effects of TMP on PCA increment induced by thrombin(P<0.05).Immunohistochemical analysis demonstrated that NF-κB translocation from cytoplasm to the nucleus was found after treatment of endothelial cells with thrombin.TMP inhibited thrombin-induced NF-κB translocation from cytoplasm to the nucleus.Conclusion NO pathway participates in the inhibitory effect of TMP on the expression of TF induced by thrombin.TMP can inhibit TF expression induced by thrombin through suppressing NF-κB activation.

Abstract:Aim To study the mouse bone marrow-derived immature CD11b⁺Gr-1⁺ myeloid progenitor cells in mice stimulated by acute inflammatory LPS,and induced to differentiate into macrophage-like cells phagocytized oxidized low density lipoprotein(ox-LDL)to form into foam cells.Methods Mice were injected with lipopoly saccharide(LPS)(5 μg/g weight,IP),24 hours later flow cytometry was used to analyze bone marrow,spleen,and peripheral blood CD11b⁺Gr-1⁺ myeloid precursor cells,CD11b+ Gr-1-mononuclear cells,and CD11b-Gr-1+ granulocyte changed in proportion.Experimental in vitro formation of foam cells,mononuclear cells obtained from mice bone marrow were cultured in DMEM + fetal bovine serum(FBS)medium,co-cultured with granulocyte-macrophage colony-stimulating factor(GM-CSF)for 48 hours to differentiate into monocyte /macrophage-like cells,then co-cultured with ox-LDL(100 mg /L)for 48 hours to form lipid burdened foam cells.Oil red O staining identified foam cells.Results(1)LPS intraperitoneal injection can promote the CD11b + Gr-1+ myeloid precursor cells from bone marrow to mobilizate significantly and to release into the peripheral tissue;the amount of CD11b⁺Gr-1⁺ myeloid precursor cells and CD11b+ Gr-1-mononuclear cells in spleen and circulating pool increased significantly.(2)CD11b⁺Gr-1⁺ myeloid precursor cells which were isola-ted from bone marrow were co-cultured with GM-CSF differentiated into monocyte /macrophage-like cells,and then were incubated with ox-LDL to form lipid burdened cells(foam cells).Oil red O staining showed the cytoplasm of foam cells with red-dyed,large lipid droplets,nuclear were squeezed by the lipid droplets to the corner.Conclusion Acute inflammatory stimulus LPS can mobilize the mouse bone marrow CD11b⁺Gr-1⁺ myeloid precursor cells to release to the circulation and peripheral tissue.CD11b⁺Gr-1⁺ myeloid precursor cells can be induced to differentiate and phagocytize ox-LDL to form into foam cells.

Abstract:Aim To explore the effect of Buyanghuanwu decoction(BYHWD)on angiogenesis in rats after focal cerebral ischemia.Methods The model of focal cerebral ischemia in rats was reproduced by middle cerebral artery occlusion.Rats were randomly divided into navie,shame-operated,ischemia,Buyanghuanwu decoction(BYHWD),ED and BYHWD+ED group.Animals were received BrdU-labeled and killed at 1,7,14 and 28 day point after operation.BrdU and vWF were measured by immunohistochemical staining.Results There was a certain BrdU or vWF positive cells in normal brain,after cerebral ischemia BrdU positive cells were increased and reached the peak at 7 day.The expression of BrdU or positive cells of ED group were less than the others remarkably at the same time point(P<0.05).BYHWD can significantly increase the expression of BrdU or vWF.The increase was statistically significant at 7 and 14 day point after ischemia(P<0.05).The expression of BYHWD+ED groups was more than model and ED group at 7 day time point(P<0.05),but less than BYHWD group(P<0.05).Compared to the other groups,there was statistical significance on BYHWD for decreasing the number of nerve function at 7 and 14 day points(P<0.05).The effection of decreasing nerve function number on BYHWD+ED was better than model and ED groups(P<0.05),but less than BYHWD(P<0.05).Conclusion BYHWD may promote the angiogenesis in rats after focal cerebral ischemia.BYHWD can partly promote the angiogenesis which ED restrained.The result shows that it affects ischemia by other ways.

Abstract:Aim To observe the effect of rosiglitazone on apoptosis and expression of Phospho-Smad2/3 of thoracic aorta vascular smooth musle cell(VSMC)of hypercholesterol rat in vitro.Methods Primary cultures of rat VSMC were obtained enzymatically from dissociated hypercholesterol SD rat thoracic.Cells at passage five through eight were used in this experiment.After VSMC were serum-starved for 24 hours,they were randomly divided into two parts:part 1,cells were subdivided into four groups:①control group,②rosiglitazone group(concentration of rosiglitazone was 100umoll in this experiment),③rosiglitazone + GW9662 group,④rosiglitazone + anti-TGF-β1 group,the expression of p-Smad2/3 after 1 hour was detected by Western-blot.The apoptosis of VSMC was observed by flow cytometry after 24 hours;Part 2,cells were subdivided into two groups:①control group,②rosiglitazone group,expression level of p-Smad2/3 after 0,0.5,1,2,6,12,24 hours were detected by Western-blot.Results Our experiment show that the rate of apoptosis in VSMC treated with rosiglitazone was higher than control group(P<0.05)after 24 hours.The rate of apoptosis in VSMC in the groups treated with rosiglitazone + GW9662 or rosiglitazone + anti-TGF-β1 were higher than the group treated with rosiglitazone(P<0.05),from this we may conclude that GW9662 and anti-TGF-β1 would partly reverse the apoptosis of VSMC induced by rosiglitazone.The expression levels of p-Smad2/3 in the group treated with rosiglitazone were higher than the control group after 0.5 hour(P<0.05),and the expression level of p-Smad2/3 reached the highest in 1 hour(P<0.05)then decreased fast after top(P<0.05),from this we may conclude that rosiglitazone was able to induce VSMC expression p-Smad2/3.Furthermore,the levels of p-Smad2/3 in the group treated with rosiglitazone was higher than the groups treated with rosiglitazone + GW9662 or rosiglitazone + anti-TGF-β1,from this we may conclude that the GW9662 and anti-TGF-β1 both could partly reverse the expression levels of p-Smad2/3 in VSMC induced by rosiglitazone.Conclusion The apoptotic effect of rosiglitazone in VSMC would be mediated by a mechanism that includes the activation of PPAR-γ,inducing the apoptosis of VSMC by up-regulation of the expression level of the P-Smad2/3.

Abstract:Aim CXCL16 can be a potential player in atherogenesis.To investigate the effects of Fenofibrate on atherosclerosis and CXCL16 expression.Methods ApoE knockout mice were divided into two groups depending on treating with fenofibrate or distilled water.After 8 weeks all mice were euthanized,and ELISA was used to detect serum CXCL16 level.Aorta paraffin sections were performed with HE stain to observe and analyze atherosclerotic lesion.Expressions of CXCL16 and CXCR6 were detected by immunohistochemistry and analyzed by digital quantitative analysis software.Real-Time PCR was used to quantify CXCL16 mRNA expression.Results The atherosclerotic lesion and the expression of CXCL16 and CXCR6 were alleviated in fenofibrate group than that in control.CXCL16 mRNA expression was significantly decreased in Fenofibrate group.Conclusion Fenofibrate attenuated atherosclerosis and down-regulated CXCL16 protein and mRNA expression in ApoE knockout mice,which were independent of its cholesterol-lowering effect.

Abstract:Aim To investigate the effect of atorvastatin on serum Ang(1-7)concentration and p-ERK1/2 protein expression level in left ventricular hypertrophic myocardium in the hypertensive rats with abdominal aortic constriction,and to explore the underlying mechanism.Methods Fifty adult male SD rats were randomly divided into following five groups(n=10):sham group,model group,10 mg/(kg·d)atorvastatin group,30 mg/(kg·d)atorvastatin and 20 mg/(kg·d)valsartan group.Drugs were dissolved in physiological saline and orally administrated by gavage from day 1 after operation until four weeks.Systolic blood pressure(SBP)was taken before and after administration by 2 weeks and 4 weeks by tail-cuff method.Rats were sacrificed after 4 weeks,and body weight(BW),left ventricular weight(LVW),left ventricular weight index(LVWI)were measured;the average diameter of cardiomyocytes were measured and the changes of cardiac histopathology were observed by HE staining;serum Ang(1-7)concentration was determined by enzyme-linked immunosorbent assay(ELISA);p-ERK1/2 protein expression level in myocardic tissue was detected by Western blotting.Results SBP in 10 mg/(kg·d)and 30 mg/(kg·d)atorvastatin group were significantly lower than that in model group(P<0.01);SBP in 30 mg/(kg·d)atorvastatin group was significantly lower than that in 10 mg/(kg·d)atorvastatin group(P<0.01);SBP in valsartan group was significantly lower than that in 10 mg/(kg·d)and 30 mg/(kg·d)atorvastatin group(P<0.01).Compared with model group,LVWI was markedly higher than that among sham group,30 mg/(kg·d)atorvastatin group and valsartan group(P<0.01).LVWI in 30 mg/(kg·d)atorvastatin group was markedly lower than that in 10 mg/(kg·d)atorvastatin group(P<0.05).Compared with model group,mean diameter of cardiomyocytes were significantly higher than that among sham group,30 mg/(kg·d)atorvastatin group and valsartan group(P<0.01);there was no difference of average diameter of cardiac myocytes between 10 mg/(kg·d)atorvastatin group and model group(P>0.05).Serum Ang(1-7)concentration in model group were markedly lower as compared to that among 10 mg/(kg·d)atorvastatin group,30 mg/(kg·d)atorvastatin group and valsartan group(P<0.01).Serum Ang(1-7)concentration in 30 mg/(kg·d)atorvastatin group and valsartan group were markedly higher as compared to that in 10 mg/(kg·d)atorvastatin group(P<0.05).Compared with model group,the expression of p-ERK1/2 protein among 10 mg/(kg·d)atorvastatin group,30 mg/(kg·d)atorvastatin group and valsartan group were significantly downregulated(P<0.01),but higher than that in sham group.Conclusion Atorvastatin can reverse myocardic remodel in the hypertensive rats with abdominal aortic constriction,which may be related to reducing p-ERK1/2 protein expression level in pressure overload-induced cardiac hypertrophy tissue.

Abstract:Aim To explore the impact of multifactorial intervention on incidence of subclinical atherosclerosis(subAs)in patients with newly-diagnosed type 2 diabetes(T2DM).Methods In the prospective study,141 patients with newly-diagnosed T2DM without subAs were designed to experience the prospective targeted multifactorial intervention,including intensive control of blood glucose,blood pressure,blood lipids and body weight.The influences of multifactorial intervention and change of MS score on incidence of subAs after 6 years were analyzed.Results MS scores after 1 year intervention were significantly improved(P<0.01).The incidence rate of patients whose MS scores remained equal to or greater than 2 after 1 year intervention was significantly higher than those whose MS scores were 0 or 1 after 1 year intervention(P<0.05).The incidence rate of those whose MS scores remained 2 after 1 year intervention was 74.1%(20/27),while the incidence rate of those whose MS scores remained 3 after 1 year intervention was 100.0%(6/6).Multiple stepwise Logistic regression analysis showed that after adjustment of age and sex,MS score after 1 year intervention is independent variable of incidence of subAs after 6 years(OR=1.89,95%CI 1.19～3.01,P<0.01).Further analysis revealed that after adjustment of age and sex,central obesity after 1 year intervention was the most marked factor on subAS after 6 years among all the MS components except for hyperglycemia(OR=2.45,95%CI 1.19～5.07,P<0.05).Conclusion The early-stage metabolic syndrome intervention efficacy may predict long-term subAs outcome in patients with newly-diagnosed T2DM.Central obesity is the most important factor which deteriorates long-term subAs.

Abstract:Aim To study relationships between the carotid intima-media thickness(IMT)and serum malondialdehyde(MDA),superoxide dismutase(SOD)activity in the patients of impaired glucose regulation(IGR)and the effects of probucol on MDA,SOD and carotid IMT.Methods 50 subjects with Type 2 diabietes mellitus(T2DM),24 with IGR and 28 with normal glucose tolerance(NGT)were recruited in the study.Carotid IMT were assessed by the high-resolution B-mode ultrasound unit.Serum SOD was measured by xanthine oxidase method and the serum MDA by thiobarbituric acid method.Plasma endothelin-1(ET-1)was detected by radioimmunoassay.All the patients with T2DM or IGR were randomly divided into treatment group and control group.The treatment group received probucol(0.5 g,twice a day)on the base of previous treatment,while the control group only kept their routine treatment.The examinations were repeated in 12 weeks after treatments.Results Carotid IMT of T2DM group and IGR group were significantly higher than that of NGT group(P<0.01).Compared with that in subjects of NGT,the MDA and ET-1 level were increased in patients of T2DM or IGR(P<0.01),and ET-1 was also significantly different between the T2DM and IGR groups(P<0.01).While serum SOD activity showed a significant difference among the three groups.It was found that T2DM group was the lowest,IGR group followed by,and NGT group the highest(P<0.01).Paper showed that carotid IMT kept positive with MDA,ET-1,FBG,PBG,duration,HbA1c and LDLC(P<0.05),while negative with SOD in all the groups.In multiple linear stepwise regression,MDA,ET-1 and LDLC showed a significant association with carotid IMT.After intervention with probucol,MDA and ET-1 decreased,while SOD activities increased.Conclusions The study suggests that there have been disorders of endothelial function and oxidative system during the prediabetic state.Probucol may inhibit oxidative stress,improve endothelial function and provide a new idea for the prevention of early atherosclerosis in IGR.

Abstract:Aim To evaluate expression levels of the 5 kinds of antimicrobial peptide genes,cathelicidin(CAMP)and alpha-defensin 1-4(DEFA1-4)in peripheral blood mononuclear cells(PBMC).Methods Sixty-one patients with coronary artery disease(CAD)who had stable effort angina pectoris and had ≥50% diameter stenosis in left main coronary artery or at least one major coronary artery were involved in this study.Controls(n=53)were those with chest pain,abnormal ecletronic cadiogram or abnormal echocardiography,but had a smooth coronary angiogram(CAG).Venous blood was obtained before CAG for RNA isolation and routine blood count.Ten μg/patient of the total RNA were used for individual cDNA preparation.Expression levels of genes in individuals were evaluated by quantitative real-time RT-PCR.Results WBC count and subset counts were not different between CAD and control group,except that relative lymphocyte count in percentage was lower in the former than that in the later(27.2%±1.2% vs 31.7%±1.5%,P>=0.02).Level of CAMP gene expression was higher in CAD than that in the control [1.21(0.98～1.55)vs 0.97(0.69～1.39),P>=0.009)].Expression levels of DEFA 1-3 genes were elevated in CAD than that in the control[0.85(0.58～1.21)vs 0.61(0.41～0.86),P>=0.003)].CAD group also presented higher expression level of DEFA 4 gene than the control group [0.78(0.52～1.43)vs 0.47(0.32～0.74),P>=0.001)].The differences of these gene expression levels were not due to variations of WBC subset counts as judged by correlational analysis(all P>0.05).CAD patients had higher hs-CRP level than the controls [2.0(1.0～4.0)mg/L vs 1.0(0.5～2.4)mg/L,P>=0.02)].Expression levels of DEFA1-3,DEFA4,CAMP were not correlated with CRP level.Conclusion Expression levels of antimicrobial peptides,alpha-defensins and cathelicidin in PBMC,may be associated with coronary artery atherosclerosis.

Abstract:Aim To explore the association of lecithin:cholesterol acyltransferase(LCAT)gene polymorphism with the occurrence of familial aggregation of cerebral hemorrhage and lipid.Methods LCAT gene 608C/T polymorphism was detected by polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP)in 10 families of cerebral hemorrhage with family history(CHFH)including 30 cerebral hemorrhage patients(CHFH-P),38 first degree relatives(CHFH-Ⅰ),31 second degree relatives(CHFH-Ⅱ),27 third degree relatives(CHFH-Ⅲ),100 patients with sporadic cerebral hemorrhage(SCH)and 100 healthy controls.Results The distribution of LCAT 608C/T gene polymorphism was in accordance with Hardy-Weinberg balance in the three groups.The CT genotype frequency and T allele frequency in familial aggregation of cerebral hemorrhage group,sporadic cerebral hemorrhage group were not significantly higher than those in control group.The serum level of high density lipoprotein cholesterol(HDLC)in 608CC genotype subgroup was significantly higher than that in 608CT genotype subgroup of the same group in familial aggregation of cerebral hemorrhage group,sporadic cerebral hemorrhage group(P<0.05).Conclusion There is probably no association of 608C/T polymorphism of LCAT gene with familial aggregation of cerebral hemorrhage in han population of Hunan province.T alleles of 608C/T are possibly associated with the metabolism of HDLC.

Abstract:Aim To investigate the effect of perindopril and amlodipine on improving the artery stiffness in patients with hypertension.Methods Patients with primary hypertension were randomly assigned to perindopril(4 mg/d)and amlodipine(5 mg/d)regimen for 6 months(n=36 each).Brachial-ankle pulse wave velocity(BaPWV)was measured by an automatic brachial ankle pulse wave velocity device before treatment,after 1 month and 6 months of treatment.Results Systolic blood pressure(SBP),diastolic blood pressure(DBP)and pulse pressure(PP)were significantly decreased in two groups(P<0.01).There were no significant changes in heart rate(HR)in two groups(P>0.05).After 1 month of treatment,BaPWV was significantly decreased in perindopril(1 572.92±230.08 cm/s)and amlodipine group(1 542.31±227.59 cm/s)compared with those before treatment(1 737.39±275.99 cm/s and 1 765.50±294.57 cm/s,respectively)(P<0.001),which also occurred after 6 months of treatment(1 484.92±226.59 cm/s and 1 432.50±217.88 cm/s,respectively)(P<0.001).And BaPWV was significantly decreased after 6 months of treatment compared with 1 month treatment in two groups(P<0.001).The changes of BaPWV in one or six months were significantly greater in amlodipine group than in perindopril group(P<0.01).The change of BaPWV was significantly greater in six months than in one month in two grops(P<0.001).Conclusion Arterial stiffness of hypertensive patients was improved post amlodipine and perindopril therapy in proportion to therapy duration.Amlodipine is superior to perindopril on improving arterial stiffness of hypertensive patients.

Abstract:Aim To investigate the contribution of three renin angiotensin system(RAS)gene polymorphisms to the presence of peripheral vascular disease(PVD)in Chinese type 2 diabetes(T2DM)patients.Methods Amount to 385 consecutive T2DM patients were examined.Fifty-six of these were determined as PVD patients for their ankle brachial index(ABI)were less than 0.9.84 non-PVD individuals were enrolled as control group.The clinic parameters and the gene polymorphisms of angiotensin converting enzyme(ACE)I/D,angiotensin Ⅱ type 1 receptor(AT1R)A1166C and angiotensinogen(AGT)M235T were measured.Logistic analysis were used to study the relationship between the parameters and the risk of PVD.Results There were differences in fibrinogen(Fbg),serum creatinine(Scr)and high-sensitivity C-reactive protein(hs-CRP)between cases and controls.There were no significant differences in the genotypes and allele frequencies of the three RAS gene polymorphisms between two groups.However,in the T2DM patients with D allele of ACE I/D,the prevalence of PVD significantly increased when they had T allele of AGT M235T at the same time.Logistic regression analysis showed that Fbg,hs-CRP,and AGT M235T were the risk factors of PVD.Conclusion Inflammation factors such as hs-CRP and Fbg are involved in the development of PVD in the T2DM groups.Although the role of single gene polymorphism of RAS is limited,the interaction of the three RAS gene polymorphisms may have significant effect on the risk of PVD in T2DM patients.The individuals with T2DM presenting with D allele of ACE I/D are likely to have higher risk of PVD when they have T allele of AGT M235T at the same time.

Abstract:Aim To explore the relationship between lipoprotein-associated phospholipase A2(LP-PLA2)gene A379V polymorphisms and coronary heart disease(CHD)by Meta-analysis.Methods PubMed,Elsevier SDOS,Vip Chinese Periodical Database,Wanfang Chinese Periodical Database and Chinese Bio-medicine Database were searched for the case-control study on the association of LP-PLA2 gene A379V polymorphisms with CHD.All articles were strictly evaluated and screened according to inclusion criteria,and meta-analysis were perfomed for the included articles using RevMan 5.0 and Stata 10.0 software.Results Seven case-control studies involving 6 718 patients with CHD and 3 824 controls were included.The results of meta-analysis showed that there was not a significant difference bewteen CHD patients carrying VV/AA and VA/AA of LP-PLA2 gene A379V and controls(P>0.05),the pooled OR(95%CI)respectively were 0.98(0.66～1.46)and 0.98(0.89～1.07).The results of subgroup meta-analysis according to the race showed that the significant differences were not found in the Asian and the European subgroup(P>0.05),the pooled OR(95%CI)of VV/AA of LP-PLA2 gene A379V in the Asian and European subgroup respectively were 1.15(0.50～2.61)and 0.89(0.68～1.17),the pooled OR(95%CI)of VA/AA respectively were 1.11(0.96～1.27)and 0.88(0.66～1.18).Conclusion More evidence is needed to prove the relationship between LP-PLA2 gene A379V polymorphisms and CHD.

Abstract:Caveolae is special invaginations in the plasma membrane,while caveolin is the marker protein of caveolae,which plays a role in the maintenance of caveolae structure and a variety of cellular processes,including endocytosis,cholesterol balance and signal transduction.Caveolin-1 is rich in many types of cells such as endothelial cells,smooth muscle cells,and plays an important role in angiogenesis and proliferation of smooth muscle cells.

Abstract:Diabetic subjects exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis.However,its mechanisms are still poorly understood.There is evidence to suggest that oxidization of low density lipoprotein(LDL)accelerated the progression of diabetic vasculopathy.Lectin-like oxidized low density lipoprotein receptor-1(LOX-1)is a newly identified receptor for oxidized LDL and it is up-regulated in diabetic condition.Some studies have shown that drugs commonly used in the treatment of diabetic patients inhibit endothelial LOX-1 expression.This review summarizes the function of LOX-1 in diabetic macrovascular disease,its regulation mechanisms and therapeutic approaches.