Abstract:Atherosclerosis(As) is a complex process where both of cholesterol accumulation and inflammation in vessel wall play crucial roles in its development.ATP-binding cassette transporter A1(ABCA1) is an integral cell membrane protein that exports cholesterol from cells and suppresses vascular inflammation via binding of the apolipoprotein AⅠ(apoAⅠ).ABCA1 mutations in human can reduce plasma HDL levels and increase the risk for cardiovascular disease.Genetic knockout of ABCA1 in animal not only affect plasma HDL levels but also impair pancreatic β cell function,inflammation and promoting the progress of atherosclerosis.Inflammatory cytokines and metabolites inhibit ABCA1 protein and decrease cholesterol export from macrophages,raising the possibility that an impaired ABCA1 pathway contributes to the enhanced atherogenesis associated with common inflammatory and metabolic disorders.The ABCA1 has therefore become a promising new therapeutic target for treating atherosclerosis.

Abstract:Aim To observe the effect of Salvianolic acid B(SalB) on atherosclerotic plaque stabilization in diabetic atherosclerosis animal models prepared from apolipoprotein E(ApoE) gene knock-out mice treated by intraperitoneal injection of STZ and high fat diet.Methods Fifty two-month female ApoE gene knock-out mice were injected with STZ and fed with high fat diet for 12 weeks.Then fasting blood glucose(FBG) level was measured and forty diabetic atherosclerosis mice were selected for the following treatment experiment.Diabetic atherosclerosis mice were randomly divided into four groups.Each group was fed with same high fat diet and intragastrically administrated with different drugs for 8 weeks,named model group(distilled water),SalB high dose group(160 mg/(kg·d)),SalB medium dose group(80mg/(kg·d)) and Lovastatin group(2.3 mg/(kg·d)).Then frozen sections and paraffin sections of mice aortas were made.The lipid core area,thickness of fibrous cap,incidence of plaque erosion and the number of neovascularization in atheromatous plaque were measured by Sudan III staining,MASSON staining and immunohistochemistry staining. Results Compared with the model group,both the level of FBG and total cholesterol(TC) in the SalB high dose group and Lovastatin group reduced significantly(P<0.05).Compared with the model group,both the level of triglyceride(TG) and low density lipoprotein cholesterol(LDLC) in the SalB medium dose group,SalB high dose group and Lovastatin group reduced significantly(P<0.05),whereas the level of high density lipoprotein cholesterol(HDLC) increased significantly(P<0.05).Compared with the model group,lipid core area,the number of neovascularization in atheromatous plaque and the incidence of plaque erosion in the SalB medium dose group,SalB high dose group reduced significantly(P<0.01),whereas average thickness of fibrous cap became thicker significantly(P<0.01).Conclusions SalB may stabilize the diabetic atherosclerotic plaques by increasing average thickness of fibrous cap and decreasing lipid core area,incidence of plaque erosion and neovascularization in atheromatous plaque.

Abstract:Aim To investigate the effects of hydrogen sulfide on ox-LDL-induced apoptosis in human umbilical vein endothelial cells(HUVEC) and the mechanisms involved.Methods The HUVEC were incubated with ox-LDL for 24 hours after treatment with NaHS at different concentrations(25,50,100,200 μmol/L) for 24 hours or for different incubation time(6,12,24 hours) at the concentration of 50 μmol/L.The apoptotic alterations of HUVEC were observed by Hoechst 33258 staining and flow cytometry(FCM),respectively.The change of mitochondrial membrane potential(MMP) and intracellular reactive oxygen species(ROS) generation were detected by Dihydrohodamine123(DHR123) staining and rhodamine123(Rh123) staining.Results Pre-treatment with NaHS remarkably inhibited apoptosis induced by ox-LDL in HUVEC in a time-and concentration-dependent manner(all P<0.01).The decrease of MMP and increase of the intracellular ROS generation in HUVEC induced by ox-LDL were significantly prohibited by treatment with NaHS or N-acetyl-L-cysteine(NAC)(all P<0.05).Conclusions H2S inhibits apoptosis induced by ox-LDL in HUVEC which is involved in preservation of mitochondrial membrane potential and attenuation of the intracellular ROS generation.

Abstract:Aim To investigate the effects of intermittent high glucose on cell proliferation and the expressions of apoptosis proteins in rat vascular smooth muscle cells(VSMC).Methods Rat VSMC were incubated with constant high glucose or intermittent high glucose.VSMC proliferation was evaluated by MTT assay.The cell cycle was examined by flow cytometry.The protein expressions of Bcl-2 and Bax were studied by Western blotting.Results Compared with constant high glucose,intermittent high glucose significantly stimulated cell proliferation,enhanced transition of cultured VSMC from the G0/G1 phase to the S phase and upregulated the ratio of Bcl-2/Bax.Conclusions Intermittent,rather than constant,high glucose,could significantly promote VSMC proliferation and induce apoptosis by regulating the cell cycle and modulating the apoptosis-regulatory proteins,indicating its stronger proatherogenic role in diabetic macrovascular disease.

Abstract:Aim To study the expression of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) and interleukin-1β(IL-1β) in normal human coronary artery and atherosclerosis and the relationship between LOX-1 and IL-1β.Methods Immunohistochemistry was used to detect the expression of LOX-1,IL-1β,CD68 and smooth muscle actin on the tissue containing 15 normal coronary artery,48 atherosclerotic coronary arteries.Results The expression of LOX-1 and IL-1β in normal coronary artery was negative.Positive expression rates of LOX-1 and IL-1β were 47.5%(23/48) and 18.8%(9/48) in atherosclerotic coronary arteries,respectively.The expression mainly locates in the membrane of endothelial cells,macrophages smooth muscle cells and foam cells.Positive expression rates of LOX-1 were higher in atherosclerosis coronary artery with stenosis≤50% group(61.5%) than stenosis>50% group(31.8%).The expression of LOX-1 in intima was stronger than in media(P=0.044),and a positive association existed between LOX-1 and IL-1β in atherosclerosis(r=0.519,P=0.001).Conclusions Besides endothelial cells,LOX-1 is also expressed on smooth muscle cells and monocyte/macrophages,although the expression level is relatively low.It may appear in the early stages of atherogenesis.Positive association between LOX-1 and IL-1β in atherosclerotic coronary artery suggests that they play an important role in development and progression of atherosclerosis.

Abstract:Aim To investigate the effect of glucagon-like peptide-1 receptor agonist Exenatide on vascular endothelial dysfunction in diabetes mellitus rats.Methods 34 Healthy male Wistar rats were randomly divided into 4 groups: control group,diabetes model group,low dose of Exenatide treatment group(0.3125 μg/day),and high dose of Exenatide treatment group(0.625 μg/day).The last three groups were experienced oral glucose tolerance test and fasting insulin level detection after administrated with high fat emulsion for 14 days.After that diabetes mellitus models were established by streptozotocin injected intraperitoneally,with fasting glucose level≥11.8 mmol/L as a model successful marker.After treatment with Exenatide(injected hypodermically) for 45 days,fasting glucose levels were detected.Thoracic aortas were isolated to detect the responses to norepinephrine,acetylcholine and sodium nitroprusside.The expression of von Willebrand factor was detected by immunohistochemistry.Results After high fat emulsion administration for 14 days,the results of oral glucose tolerance test were abnormal,the glucose levels at every time-point were elevated significantly compared with control group rats(P<0.01).Besides that,both fasting insulin levels [(49.2±13.0)×10-3 μU/L] and homeostasis model assessment of insulin resistance index(11.7±3.5)were higher than control group[(35.7±4.7)×10-3 μU/L,7.7±1.1,both P<0.05],all these implied that insulin resistance arose.Compared with control group(4.6±0.4 mmol/L),the fasting glucose levels of diabetes model group(23.3±1.9 mmol/L)were increased significantly,both low dose(20.9±1.4 mmol/L)and high dose(20.2±1.4 mmol/L)of Exenatide treatment could attenuate the elevated fasting glucose levels(P<0.05,P<0.01 respectively).The responses to acetylcholine(P<0.01,P<0.05)and low-dose(10-8 mol/L and 10-7 mol/L) sodium nitroprusside(P<0.05)and the expression of von Willebrand factor were decreased significantly in diabetes model group.Except of response to sodium nitroprusside,two other parameters were improved obviously after treatment with either low dose or high dose of Exenatide(both P<0.05).There was no significant difference in response to norepinephrine among groups.Conclusion Exenatide treatment could reduce blood glucose level and attenuate the vascular endothelial dysfunction in diabetes mellitus rats.

Abstract:Aim To investigate the effects of platelet-derived growth factor(PDGF) on migration and matrix metalloproteinases-2(MMP-2) expression in vascular smooth muscle cells(VSMC).Methods After treated with PDGF 0 min,20 min and 6 hours,the ability of cell migration was measured using microscope,and MMP-2 activity was assayed by gel zymography.Furthermore the expression of MMP-2 was screened by using Chip and confirmed by reverse transcription polymerase chain reaction(RT-PCR).Results The ability of cell migration was improved by PDGF.It was 2.13-fold for 20 min treatment and 3.09-fold for 6 h treatment compared to without PDGF treatment,respectively(P<0.05,n=3).The activity of MMP-2 was also significantly increased 1.62-fold and 2.87-fold for 20 min and 6 h treated by PDGF compared with 0 min,respectively(P<0.01,n=3).The mRNA expression of MMP-2 was 1.54-fold,2.2-fold higher in cultured with PDGF at 20 min and 6 h than 0 min,respectively(P<0.05,n=3).Conclusion Our data indicate that PDGF improve vascular smooth muscle cell migration via inducing MMP-2 expression and enhancing MMP-2 activity.

Abstract:Aim To investigate the vasodilatory mechanisms of C-type natriuretic peptide(CNP) via the natriuretic peptide receptor-C(NPR-C) pathway.Methods This study was performed on the porcine coronary artery rings,and the tension changes of coronary artery ring were recorded with the presence of CNP or NPR-C agonist(cANF4-23),further NPR-C antagonist(cANF4-28),Gi protein blocker(pertussis toxin,PTx) and four types of potassium channel blocker were used to explore the vasodilatory mechanisms.Results Vasorelaxant activities to 10-6mol/L CNP and cANF4-23 were 36.51%±3.96% and 42.37%±17.60% respectively(P>0.05);cANF4-28 or PTx can attenuate the action of both CNP and cANF4-23(P<0.05);Tetraethylammonium,Glibenclamide or BaCl2 all can attenuate the relaxant activity of CNP(P<0.05),but only BaCl2 decreased the vasodilatory action of cANF4-23(P<0.05).Conclusions Activation of the G protein-coupled inwardly-rectifying potassium channel(GIRK) maybe account for the vasodilatory action of CNP via the NPR-C pathway.

Abstract:Aim To study possible clinical relationships of myeloperoxidase(MPO) and carotid atherosclerosis in non-diabetic patients with maintenance hemodialysis(MHD).Methods Levels of plasma MPO and serum elastase(ELT) of non-diabetic patients with MHD were determined by ELISA.Carotid intima-media thickness(IMT),quantity and area of carotid plaque were measured by B-mode ultrasonography.Results There was no significant difference of serum ELT before and after hemodialysis(HD).Plasma MPO was significantly higher after HD than before HD(P<0.01).There was positive correlation between age,MPO level before HD and carotid IMT(P<0.01).There was no correlation between the levels of plasma MPO after HD and serum ELT or carotid IMT.Conclusions MPO level before HD contributed to carotid atherosclerosis in patients on MHD.In contrast,there was no relation between higher MPO level after HD and carotid atherosclerosis.This finding suggests that increased plasma MPO levels after HD do not reflect increased activation/degranulation of leukocytes and supports the view that the increase in circulating MPO reflects the heparin-induced release from the atherosclerotic vascular wall.

Abstract:Aim To compare the effects of probucol combined with atorvastatin and atorvastatin only on serum oxidized low density lipoprotein(ox-LDL)and ox-LDL antibodies(ox-LDL-Ab) levels.Methods Forty eight patients with coronary heart disease were assigned to atorvastatin only group(20 mg/d of atorvastatin,n=22) or combined therapeutic group(20 mg/d of atorvastatin and 1.0 g/d of probucol,n=26) in a randomized manner.Serum levels of ox-LDL and ox-LDL-Ab were detected before and after treatment.Results After treated with atorvastatin only and combined therapy the levels of serum LDL,ox-LDL,TC and TG were significantly decreased(P<0.01),and those in combined therapy decreased even more markedly(P<0.05).Alone in the treatment group ox-LDL antibodies had no significant effect(P>0.05).Combined treatment group can significantly reduce the level of ox-LDL antibody(P<0.01).Conclusions Both atorvastatin alone and atorvastatin combined probucol can decrease the levels of ox-LDL in patients with coronary heart disease,and those in combined therapy decreased even more markedly.Alone in the treatment group ox-LDL antibodies had no significant effect.But combined treatment group can significantly reduce the level of ox-LDL antibody levels.

Abstract:Aim To investigate the relationship between small and dense low-density lipoprotein cholesterol(sdLDLC) and the carotid atherosclerotic plaque in Chinese population.Methods The serum level of sdLDLC was examined by the automatic analyzer in 166 patients.They were all examined with the carotid colour Doppler flow imaging,and were grouped as plaque group(n=86) and no plaque group(n=80) according to the result of duplex colour Doppler flow imaging.Patients of the two groups were compared in the level of some possible risk factors including age,sex,drinking,smoking,hypertension,diabetes mellitus,and total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDLC),high-density lipoprotein cholesterol(HDLC).Logistic regression model was applied in the screening of risk factors.Results The mean age,mean total cholesterol,mean triglyceride,incidences of hypertension and diabetes mellitus were significantly higher in patients with carotid plaques than in patients without by single-factor analysis.No significant difference of sex,drinking,smoking,the mean value of low-density lipoprotein cholesterol,high-density lipoprotein cholesterol was found between two groups.Logistic milti-factor regression analysis showed that age(OR=1.10,P<0.01),hypertension(OR=2.81,P<0.05),diabetes mellitus(OR=2.74,P<0.05) and sdLDL-C(OR=3.8,P<0.001) were involved in the regression equation statistically.Conclusions The formation of the carotid atherosclerotic plaque is the interactional result of multiplicate factor.High TG and high TC are the related risk fac-tors of carotid plaque.Age,hypertension,diabetes mellitus and sdLDLC are the possible independent risk factors for carotid plaque.

Abstract:Aim To investigate the characteristics of epicardial adipose tissue in type 2 diabetes patients with metabolic syndrome.Methods 120 type 2 diabetes patients were included.Anthropometric measurements including height,weight,waist circumference,hip circumference and blood pressure were taken.Fasting venous blood was obtained and fasting plasma glucose,glycation hemoglobin,triglyceride(TG) and high density lipoprotein cholesterol(HDLC) were measured.Body fat composition,lean and epicardial adipose tissue(EAT) were analyzed by dual-energy-X-ray absorptiometry and echocardiogram,respectively.Multivariate Logistic regression analysis was used to estimate the strength of association between EAT and various factors.Results Patients with MS had greater waist circumference,Waist-to-Hip Ration,triglyceride,total body fat,android fat deposition,EAT and prevalence of hypertension and coronary artery disease than patients without MS.Waist circumference,triglyceride and android fat deposition were independent risk factors for increased ETA,while HDLC was an independent protective factor.Conclusions Type 2 diabetes with metabolic syndrome patients have increased EAT,which is significantly associated with waist circumference,triglyceride,android fat deposition and HDLC.

Abstract:Aim To evaluate the relationship between ambulatory pulse pressure(ABP) and ischemic stroke in the very elderly hypertension patient.Methods 131 patients with essential hypertension were divided into two groups: 57 patients with ischemic stroke and 74 patients without ischemic stroke.ABP,casual blood pressure(CBP) and cerebral CT(or MRI) were examined in all subjects.The data of age,gender et al,were obtained for each of the patients.Results The age,gender had no statistical significance between the two groups.Systolic blood pressure(SBP),pulse pressure(PP),isolated systolic hypertension(ISH)were significantly higher in the ischemic stroke group than in group without ischemic stroke(166.82±24.00 mmHg vs 154.81±23.71 mmHg,81.29±17.44 mmHg vs 72.41±17.32 mmHg,P<0.01);There was significant difference in day mean systolic blood pressure(dMSBP),day mean diastolic blood pressure(dMDBP),circadian rhythm between the two groups(137.57±19.66 mmHg vs 132.00 ±15.09 mmHg,71.92±12.47 mmHg vs 68.29±10.82 mmHg,P<0.05).Conclusion Abnormal blood pressure especially SBP,PP,and circadian rhythm have direct connection with ischemic stroke in the very elderly hypertension patient.

Abstract:Aim To investigate the correlation between metabolic syndrome(MS) and benign prostatic hyperplasia(BPH).Method We selected 197 cases who were diagnosed as BPH in the first affiliated hospital of Xinjiang Medical University Cadres Ward,the male subjects and Urology,and from November 2008 to October 2009 to investigate the correlation between MS and BPH.Results Analysis showed that the MS and its components such as: obesity,HDL,high blood sugar,hypertension had statistical differences with BPH(P<0.05).The prostatic volume in group of BPH with hypertension with diastolic biood pressure ≥90 mmHg was significantly higher than those with diastolic blood pressure <90 mmHg(P<0.05).The IPSS and prostatic volume in group of BPH with abnormal free blood glucose were significantly higher than those with normal free blood glucose(P<0.05).Conclusion The MS is closely related with BPH,which may be a risk factor of BPH.

Abstract:Aim To examine the morphological characteristics and the composition of atherosclerotic plaque in carotid arteries using multislice spiral computer tomography(MSCT) and to investigate the relationship between these plaque features and cerebral infarction.Methods The MSCT angiography images of 60 patients with carotid related cerebral infarction were analyzed retrospectively,and the degree of carotid stenosis,plaque components and morphological characteristics was measured using automated plaque analysis software.Results The ratio of moderate and above luminal stenosis(80.0% vs 45.0%,χ2=15.68,P<0.05),the ratio of soft plaques and mixed plaques(68.9% vs 38.3%,χ2=12.54,P<0.05),the ratio of irregular and ulcer plaques(77.0% vs 38.3%,χ2=20.62,P<0.05)was significantly different between infarct side and contralateral side.Conclusion Instable plaque with irregular surface can increase the risk for stroke compared with stable plaque with regular surface in carotid artery.MSCT angiography is an important and non-invasive method for carotid atherosclerotic plaque.

Abstract:Aim To evaluate the protective effect of irbesartan on renal function in elderly patients with microalbuminuria.Methods 113 old patients with microalbuminuria,who were suffered from hypertension or diabetes,were involved in the study.Patients were divided into two groups,irbesartan group or control group,all received strictly antihypertensive therapy with irbesartan or without any angiotensin-converting enzyme inhibitor(ACEI) or angiotensin receptor blocker(ARB).Results The average levels of systolic blood pressure and diastolic blood pressure in two groups decreased significantly compared with baseline levels(P<0.05).But,the levels of blood pressure had little difference between the two groups(P>0.05).Urinary α1-microglobulin and urine microalbumin in irbesartan group after treated for 12 months were significantly decreased from 18.4±6.5 mg/L to 13.5±4.2 mg/L and from 78.3±12.7 mg/L to 58.4±9.3 mg/L,respectively(P<0.05).Meanwhile,there was no such a change in control group.The serum creatinine and glomerular filtration rate changed slightly after treatment for 12 months in two groups.Conclusion Irbesartan is beneficial to reduce urinary albumin and to protect renal function in elderly patients,who suffered from hypertension or diabetes mellitus.

Abstract:Aim To study the relationship between carotid atherosclerotic plaques and transient ischemic attack(TIA).Methods 84 cases with internal carotid artery TIA were tested by doppler ultrasound technology in extracranial carotid artery.The testing analysis indicators are distribution,narrow degree and the ultrasonic parting of extracranial carotid atherosclerotic plaques.And comparing and studying the symptoms side to asymptomatic lateral.Results The soft spot was the most frequent,followed by mixing spot and ulcer spot in TIA patients with extracranial carotid atherosclerotic plaques,and the differences were significant(P<0.01).There was no obvious difference in hard spot and flat spot.The incidence in Asymptomatic lateral patches(60.34%) was obviously higher than symptomatic lateral patches(39.66%),and the difference was significant(P<0.01).The moderate or above narrow incidence in Asymptomatic lateral extracranial carotid artery(29.31%) was obviously higher than symptomatic side(6.70%),and the differences were significant(P<0.01).Conclusions Extracranial carotid atherosclerosis is a significant risk factor in TIA patients.There is important reference value to evaluate extracranial carotid atherosclerosis severity and causes in TIA patients by color ultrasonic testing regularly.

Abstract:How components of metabolic syncrome(MS) progress to coronary atherosclerotic heart disease(CAD) is still unclear.Adponectin,a fat-derived plasma protein,is recently considered as a link between MS and CAD,as a number of studies reveal that decreased adiponectin level is associated with impaired endothelial-dependent vasodilation,and adponectin improves endothelial dysfunction through enhancing endothelial nitric oxide(NO) production,suppressing reactive oxygen species generation,and downregulating vascular inflammatory signaling cascade,thus adiponectin may be beneficial to prevention and treatment of MS and CAD.

Abstract:To date,atherosclerosis has been considered as an inflammatory process triggered by diverse immune cells.The cells involved in innate immunity such as monocytes and macrophages,adaptive immunity such as T cells and B cells,and cytokines secreted by immune cells all participate in the process.However,the cells involved functions differently with some promoting atherosclerosis while others inhibiting it.In human,CD14+CD16+was pro-inflammatory,whereas CD14+CD16-was anti-inflammatory.Th1and Th17 cells have a pro-atherogenic role,while Th2 and CD4+CD25+ regulatory T cells act oppositely.In recent years,antibodies targeting oxLDL were proven athero-protective in studies.It is no doubt that a further understanding of immunological mechanisms in atherosclerosis will guide effective prevention and therapeutics of this disorder.