Abstract:AimTo investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and urokinase-type plasminogen activator(uPA) in aortic atherosclerotic plaques of apolipoprotein E knockout(ApoE-/-) mice and to explore the relationship between the two.MethodsApoE-/- mice were randomized into ordinary diet fed group and high-fat diet fed group，raising for 18 weeks.At 6 weeks, 10 weeks, 14 weeks, 18 weeks mice were sacrificed and observed by HE staining of atherosclerotic plaque morphology.EMMPRIN and uPA expression in aortic atherosclerotic plaques were detected by semi-quantity RT-PCR and Western blot.RusultsAtherosclerosis model was successfully established; EMMPRIN and uPA in aorta atherosclerotic plaques were highly expressed, with statistically significant difference from normal diet group (p<0.05).Expression of EMMPRIN and uPA increased with feeding time extended.ConclusionExpression of EMMPRIN and uPA in ApoE-/- mice aortic atherosclerosis increased with plaque lesions degree of severity, both of EMMPRIN and uPA may play a role in the atherosclerotic plaques development.

Abstract:AimTo investigate the effect of telmisartan on the expression of vascular cell adhesion molecule-1(VCAM-1), Nuclear factor-κB（NF-κB）induced by homocysteine (Hcy) in human umbilical vein endothelial cells（HUVEC）and the adhesion to monocytes.MethodsCollagenase was used to isolate the endothelial cell from human umbilical vein.RT-PCR was used to examine the expression of VCAM-1 mRNA.Western blot was used to detect expression of VCAM-1 and NF-κBp65 protein.ROSE BENGAL staining technique was used to detect Mononuclear cells-endothelial cell adhesion function.ResultsThe expression of VCAM-1 mRNA，VCAM-1 protein，NF-κB p65 protein and the adhesion function to monocytes were induced by Hcy in HUVEC comparaed with the control group （p<0.01）.By comparion with the Hcy group, telmisartan (1000 nmol/L) obviously decreased the expression of VCAM-1 mRNA，VCAM-1 protein，NF-κB p65 protein and the level of endothelial cells adhesion to monocytes induced by Hcy in HUVEC（p<0.01）.NF-κB inhibitor remarkably antagonized the expression of NF-κB p65 protein， VCAM-1 mRNA and VCAM-1 protein induced by Hcy in HUVEC，and the adhesion function between mononuclear cells and endothelial cells was also decreased（p<0.01）.ConclusionTelmisartan decreased the higher expression of VCAM-1 mRNA, protein and the level of endothelial adhesion with monocytes induced by Hcy in HUVEC.The mechanism may be through inhibiting the activation of nuclear factor-κB to control inflammation and endothelial injury.

Abstract:AimTo explore the roles of regulating energy metabolism and mechanism of adenosine A1 receptor agonist inhibiting myocardial hypertrophy by means of 2-chlorinated adenosine (2-CADO) on isoproterenol induced myocardial hypertrophy in rats.MethodsHigh-dose isoproterenol subcutaneous injection to rats were used to establish myocardial hypertrophy model.Forty Sprague-Dawley rats were randomly divided into four groups with ten rats for each group: control group, isoproterenol induced myocardial hypertrophy group, isoproterenol induced myocardial hypertrophy＋2-CADO (6 mg/(kg·d), intraperitoneal injection) group, isoproterenol induced myocardial hypertrophy＋propranolol (28 mg/(kg·d), per os) group.Rats began to medicate at the second day after myocardial hypertrophy model establishment for 8 weeks.The whole heart quality index (HMI)and left heart quality index (LVMI) were detected.Left ventricular tissue was taken to observe the changes of TDM by Masson staining.Hydroxyproline (Hyp) content was determined by alkaline hydrolysis.Myocardial tissue lactate (LA) and free fatty acid (FFA) content were detected by UV spectrophotometry.Mitochondrial membrane potential (MMP) was detected by laser scanning confocal microscope.ResultsCompared with control group, in myocardial hypertrophy group HMI and LVMI were higher, the contents of Hyp, LA and FFA from left myocardial tissue were significantly increased and MMP decreased by 44%.Compared with myocardial hy-pertro phy group, in myocardial hypertrophy＋2-CADO group and myocardial hypertrophy＋propranolol group HMI, LVMI and the contents of Hyp, LA and FFA reduced, MMP increased by 50%.ConclusionsAdenosine receptor agonist 2-CADO can inhibit myocardial hypertrophy induced by isoproterenol, the mechanism may be related to improving cardiac energy metabolism and preserving MMP.

Abstract:AimTo establish the rabbit model of atherosclerotic vulnerable plaques, and study the effects of prostaglandin E1 on the angiogenesis which is induced by atherosclerosis.Methed30 New Zealand white rabbits were randomly divided into 3 groups (model group, prostaglandin E1 group, and simvastatin group), each group has 10 rabbits.The rabbit model of atherosclerotic vulnerable plaques were established, and the rabbits were given drugs to affect the disease.The abdominal aorta were processed and examined by hematoxylin-eosin (HE) staining.The angiogenesis and hemorrhage in plaques was detected.The vulnerability index was counted.Immunohistochemical staining was performed to detect the expressions of related factors.And the reverse transcription polymerase chain reaction (RT-PCR) was done to observe the expression of hypoxia-inducible factor-1α (HIF-1α) mRNA and vascular endothelial growth factor (VEGF) mRNA.ResultsCompared with the model group, the expression levels of vulnerability index and platelet-endothelial cell adhesion molecule-1 (CD31) in the prostaglandin E1 group were less (1.23±0.20 vs 2.84±0.59, p<0.05; 1.23±0.20 vs 2.84± 0.59, p<0.05).The expression levels of HIF-1α, VEGF were lower in plaques (0.252±0.032 vs 0.439±0.044, p<0.01; 0.396±0.026 vs 0.673±0.084, p<0.01).The expression levels of HIF-1α mRNA and VEGF mRNA were lower in plaques too (0.706±0.030 vs 1.183±0.134, p<0.05; 0.121±0.019 vs 0.468±0.022, p<0.05).However, the expression levels of HIF-1α and HIF-1α mRNA between the prostaglandin E1 group and simvastatin group are different (0.252±0.032 vs 0.163±0.018, p<0.05; 0.706±0.030 vs 0.763±0.018, p<0.05).ConclusionProstaglandin E1 inhibits angiogenesis of atherosclerotic vulnerable plaque, and it works by reducing the expression of HIF-1α and VEGF.

Abstract:AimTo investigate the effects of acute hyperglycemia on cerebral ischemia/reperfusion injury (CIRI) and analyze the relationship between blood glucose levels and the extent of CIRI as well as the prognosis.MethodsRats were subjected to 90 min middle cerebral artery occlusion (MCAO).To induce acute hyperglycemia, rats received 25% glucose or 0.9% sodium chloride (10 mL/kg body weight) via the intraperitoneal route 30 min before MCAO.At 24 h after reperfusion, the serum creatine kinase brain isoenzyme (CK-BB) levels, infarct volumes, brain tissue water contents, symptoms of neurological impairment, brain pathological changes and the degree of neuronal apoptosis were assessed.ResultsHyperglycemic group displayed lower survival rate and more severe brain pathological changes than the control group (p<0.05), infarct volumes, apoptosis, brain tissue water contents, the risk of intracranial hemorrhage (p<0.05), neurological deficits and the level of serum CK-BB (p<0.01) were all significantly higher than those in the control group.The levels of serum CK-BB and blood glucose concentrations displayed linear relationship before ischemia-reperfusion.ConclusionsAcute hyperglycemia aggravates cerebral ischemia-reperfusion injury possibly by increasing edema, promoting apoptosis and elevating the level of serum CK-BB.Thus, high blood glucose levels are associated with more severe brain damage and poorer prognosis.

Abstract:AimTo investigate the effect of atorvastatin on mRNA expression of liver X receptor α (LXRα) and its target gene ATP-binding cassette transporter A1 (ABCA1), sterol regulatory element binding protein-1 (SREBP-1) in human umbilical vein endothelial cells (HUVEC) after treated by lipopolysacharide(LPS).MethodsHuman umbilical vein endothelial cells were cultured in vitro with gibco 1640 medium and 10 percent fetal bovine serum and 1 percent double antibiotics, and then were plated in 6-well plates at a denisity of approximately 2×105 cells per milliliter of media to be intervened.(1)Control group: HUVEC were cultured with the completed medium involving phosphate buffered saline (PBS), and LPS treated group or control intervention group: HUVEC were treated with LPS (the terminal concentration was 100 μg/L) for 24 hours; (2)Atorvastatin intervention group or control intervention group:HUVEC were first treated with atorvastatin at different concentrations (0.1, 1.0, 10.0 μmol/L) or dimethyl sulfoxide (DMSO) for 2 hours, and then co-treated with LPS for 22 hours.The level of LXRα and its target genes mRNA expression were measured by real-time polymerase chain reaction.ResultsCompared with control group, LPS could inhibit the mRNA expression of LXRα and its target genes ABCA1, SREBP-1 in HUVEC.The differences were statistically significant (p<0.05).Compared with LPS plus DMSO group, atorvastatin could upregulate the mRNA expression of LXRα and its target gene mRNA expression in a dose-dependent manner.The differences were statistically significant (p<0.05).Meanwhile, atorvastatin could downregulate the mRNA expression of inflammatory factor and adhesion factors in a dose-dependent manner.

Abstract:AimTo investigate the effects of different dosage of atorvastatin postconditioning and its mechanisms on myocardial ischemia-reperfusion injury in GK rat.MethodsSeventy GK rats were randomly divided into seven groups (n=10 each)： sham group, ischemia-reperfusion injury (I/R) group, different dosage of atorvastatin (0.1, 0.5, 1 and 2 mg/kg) postconditioning group, atorvastatin＋LY294002.Myocardial infarct size (IS), ultrastructural change and myocardial expression of phosphorylated Akt/totalAkt were determined.ResultsMyocardial infarct size and ultrastructural damages were all reduced, myocardial Akt phosphorylation was significantly increased, and Akt was significantly activated in atorvastatin postconditioning group compared with I/R group.The effects were significant at 1 mg/kg and 2 mg/kg atorvastatin postconditioning group, and were significantly attenuated by PI3K inhibitor LY294002.ConclusionAtorvastatin postconditioning could dose-dependently alleviate myocardial ischemia-reperfusion injury in this type 2 diabetic model, which may probably be associated with the increase of the activating PI3K/Akt signaling pathway in the myocardium.

Abstract:AimThe aim of this study was to investigate the relation of traditional Chinese drug Dan Hong, C-reactive protein (CRP) and matrix metalloproteinase-1 (MMP-1).MethodsHuman THP-1 cells were induced to differentiated into macrophages with phorbol-12 myristate 13-acetate (PMA).Enzyme-linked immunosorbent assay (ELISA) was used to determine the macrophages secretes MMP-1 in peak time.Thereafter, cells were divided into three groups: control group, CRP group, Dan Hong injection group, ELISA was applied to test the MMP-1 concentration in the cell supernatant of three groups, and then MMP-1 mRNA expression at different time was tested by reverse transcription polymerase chain reaction (RT-PCR) in CRP group.At last, the protein concentration and mRNA expression of MMP-1 were analyzed.ResultsTHP-1 cell induction into macrophages was observed under the microscope, the peak of MMP-1 secretion was in 24-hour.Compared with the control group, protein and mRNA expression of MMP-1 in CRP group was up-regulated gradually with 5 mg/L, 10 mg/L, 25 mg/L, 50 mg/L CRP.The result exposed that MMP-1 level was markedly elevated in a concentration dependent fashion (p<0.05).Compared with the control group, MMP-1 ex-pression in Dan Hong injection group was lower than the control group.MMP-1 expression in Dan Hong injection group was down-regulated segmentally and dependently with 200 mL/L, 400 mL/L, 800 mL/L, 1 600 mL/L, 3 200 mL/L Dan Hong injection, but MMP-1 expression by Dan Hong injection intervention has no significance whether with CRP (50 mg/L) or not (p>0.05).ConclusionsCRP promotes the expression of MMP-1 in THP-1 derived macrophages.Dan Hong can attenuate the MMP-1 secretion in interval, and there was no difference with or without CRP.

Abstract:AimTo investigate the serum level of visfatin in the population with different obese type, and to analyse the relationship and clinical significance between visfatin and arterial stiffness.MethodsThe basic information was collected in a total of 1063 subjects who were enrolled by the physical examination center of the second people’s hospital of changzhou.Obesity measured by bioelectric impedance analysis, and divided the study population into four groups, based on percent of body fat and waist to hip ratio: normal, normal body weight but viscerally obese, excessive body weight but not viscerally obese, and excessive body weight and viscerally obese.Arterial stiffness was assessed by brachial-ankle PWV(baPWV).Fasting serum visfatin was tested by ELISA.ResultsComparison of the normal body weight group， the levels of serum visfatin and mean baPWV were significantly higher in the obese group, especially in the viscerally obese group (p<0.05).The serum levels of visfatin was positively correlated with baPWV, systolic BP, diastolic BP, hs-CRP（r=0.366, 0.217, 0.138, 0.253， respectively, p<0.05）.In a multivariate regression analysis, baPWV was independently determined by systolic BP（p<0.01）, age（p<0.01）, hs-CRP（p<0.01）, serum visfatin（p<0.01）, WHR（p<0.01）, diastolic BP(p=0.01), FPG（p=0.016）.Adjusted R² of the model was 0.765.ConclusionThe result suggest that the elevated level of visfatin is associated with systemic inflammation and artery stiffness in viscerally obese.The visfatin may act as a prediction factor in the cardiovascular disease.

Abstract:AimTo explore the relation between the genetic polymorphism cholesterol ester transfer protein (CETP) TaqIB and the stability of carotid atherosclerosis of cerebral infarction patients.Methods135 cases of cerebral infarction with vulnerable plaques and 158 cases of cerebral infarction with stable plaques were studied.Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method was adopted to determine CETP TaqIB gene polymorphism for all specimens, comparing CETP TaqIB gene polymorphism in the vulnerable plaque group with the stable plaque group, which were statistically analysed.ResultsThe proportions of B1B1, B1B2, B2B2 genotype in the vulnerable plaque group were 56.30%, 33.33% and 10.37% respectively, and were 53.80%, 36.07% and 10.13% in the stable plaque group, the difference has no statistical significance.The frequencies of B1, B2 allele in the vulnerable plaque group were 72.96% and 27.04% respectively, and were 71.84% and 28.16% in the stable plaque group, the difference also has no statistical significance in comparison.ConclusionsCETP TaqIB genetic polymorphism may have no definite relationship with the stability of carotid atherosclerosis of cerebral infarction patients.

Abstract:AimTo investigate the association between serum YKL-40 and degree of coronary artery disease (CAD) in patients with type 2 diabetes mellitus.Methods197 patients with type 2 diabetes mellitus undergoing coronary angiography because of angina-like symptoms were divided into control group (n=89) and CAD group (n=108) according to the absence or presence of significant coronary stenosis (luminal diameter narrowing of ≥50%).The degree of CAD was graded as single-, double- or three-vessel disease, and Gensini score was used to evaluate the extent of CAD.Serum YKL-40 and high sensitivity C-reactive protein (hs-CRP) levels were assessed by ELISA.ResultsCompared with control group, CAD patients were more cigarette smoker and had higher systolic blood pressure and serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDLC), apolipoprotein B (ApoB), lipoprotein (a) (Lp(a)), 2 h postprandial blood glucose (2h BG), HbA1c, YKL-40, and hs-CRP (all p<0.05).Serum YKL-40 level was increased in patients with CAD, which was more remarkable in those with two- or three-vessel disease (p<0.01), and the Gensini score of single-vessel disease was lower than that of two-disease and three-disease vessel (p<0.01).Furthermore, significant correlation between serum YKL-40 and Gensini score was observed (r=0.611, p<0.01).Multivariate Logistic regression analysis indicated that serum YKL-40 was a risk factor for CAD in patents with 2 diabtetes mellitus (OR=1.229, 95%CI was 1.086～1.427, p=0.003).ConclusionsYKL-40 may be involved in the initiation and development of atherosclerosis in diabetic patients, and serum YKL-40 level is associated with the severity of CAD in patients with type 2 diabetes mellitus.

Abstract:AimTo investigate proprotein convertase subtilisin/kexin 9 (PCSK9) gene mutations in Chinese with hypercholesterolemia.MethodsGenomic DNA was extracted from 100 cases of hypercholesterolemia and 100 healthy normal individuals with age and sex matched.Apolipoprotein B100 (Apo B100) and low density lipoprotein receptor (LDLR) mutations were excluded.All of the 12 exons of PCSK9 gene were amplified by polymerase chain reaction (PCR).The PCR products were sequenced directly.ResultsThree missense mutation (D320N, V312F and R319E), one frameshift mutation (934delGV312S), three samesense mutation (A305A, Q342Q, K125K) and one splice junction mutation (5′ splice junction site mutation in intron 2) were found in PCSK9 gene in six patients among 100 patients.ConclusionThe mutations of PCSK9 gene are maybe one reason to cause Chinese hypercholesterolemia.

Abstract:AimTo investigate the association between ambulatory pulse pressure and carotid-radial pulse wave velocity (crPWV) in elderly patients with essential hypertension.MethodAccording to the results of 24 h ambulatory pulse pressure (APP), 229 patients were divided to APP≥60 mmHg group (n＝117) and APP＜60 mmHg group (n＝112), crPWV, blood glucose and lipid profiles were recorded.ResultsThe crPWV of APP≥60 mmHg group was significantly higher than APP＜60 mmHg group (11.5±1.4 m/s vs 10.3±1.2 m/s, p<0.01).Pearson relation analysis showed that crPWV level positively correlated with age, systolic blood pressure (SBP), fasting blood glucose (FBG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), 24hSBP, dSBP, nSBP, 24hPP, dPP, nPP (r＝0.302, 0.248, 0.224, 0.306, 0.365, 0.466, 0.492, 0.372, 0.552, 0.546, 0.488, all p<0.01).Multiple linear regression showed that 24hPP were significant and independent factor for crPWV in elderly patients with essential hypertension.ConclusionThe study showed that 24hPP was closely related with atherosclerosis in elderly patients with essential hypertension.

Abstract:AimTo evaluate the long term clinical results in elderly patients(＞75 years) with coronary artery disease after percutaneous coronary intervention.MethodsFrom January 2008 to January 2010,351 patients underwent percutaneous coronary intervention in the Chinese PLA General Hospital were divided into two groups, the number of normal group (≤75 years old) was 180, the elderly group (>75 years old) was 171, general clinical data and the result of coronary angiography were recorded, the rate of myocardial infarction, repeated percutaneous coronary intervention and adverse events after percutaneous coronary intervention were detected.ResultsIn age>75 years old group, the incidence of hypertension and diabetes increased(p<0.05),they had multiple coronary artery lesion,the rate of left circumflex artery and right coronary artery lesion were significantly higher than the normal group(p<0.05), cardiac mortality, repeated percutaneous coronary intervention, coronary artery bypass rate increased significantly in elderly group(p<0.05).ConclusionMany elderly patients with coronary heart disease suffered from hypertension and diabetes,coronary artery lesions in elderly patients were more complex.Cardiac mortality, repeated percutaneous coronary intervention, coronary artery bypass rate increased in elderly group,PCI can not reduce the long-term mortality.

Abstract:AimTo evaluate the association of ATP-binding cassette transporter A1(ABCA1) gene R219K polymorphism with coronary heart disease (CHD) in Chinese Han population.MethodsCase-control studies published before 31 May 2012 about the association of ABCA1 gene R219K polymorphism and CHD 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 Egger’s test and the odd ratios of all studies were combined dependent on the result of heterogeneity test among the individual studies.The software Stata (version 11.0 ) were used for Meta-analysis.ResultsA total of twelve case-control studies were collected, 2257 cases and 2356 controls were involved in the Meta-analysis.The results indicated that the K219 was significantly associated with CHD (OR=0.66, 95%CI 0.55～0.80, p<0.0001) under dominant model and (OR=0.63, 95%CI 0.53～0.75, p<0.00001) under recessive model, respectively.No significant publication bias was found.ConclusionsR219K polymorphism in ABCA1 gene is associated with susceptibility of CHD and K allele might be a protective factor for CHD in Chinese Han population.

Abstract:AimIn this study, fluorescence labeled cholesterol (NBD-cholesterol) was used to establish a new method to evaluate the cholesterol efflux, and compared NBD-cholesterol with ³H-cholesterol in assay of cholesterol efflux.MethodsIsolated human peripheral blood monocyte cells from volunteers were differentiated into human macrophages.Human monocyte line THP-1 and mouse monocyte line J774 cells were cultured in vitro.THP-1 macrophages were incubated with different concentrations of NBD-cholesterol to choose an optimistic concentration and incubation time.NBD-cholesterol efflux rate was evaluated from three different kinds of macrophages.NBD-cholesterol uptake and efflux rate were reflected by fluorescent intensity measurement by multi-label counter.The NBD-cholesterol efflux capacity in human macrophages was estimated by the correlation to ³H-cholesterol efflux in human macrophages.ResultsNBD-cholesterol distributed rapidly into cells organelles except nucleus.Uptake of NBD-cholesterol in THP-1 macrophages was concentration dependent, but time to plateau was not dependent on concentration.NBD-cholesterol efflux rate reflected an appropriate cholesterol efflux rate in human macrophages, THP-1 macrophages and mouse macrophages.Both apolipoprotein A1 mediated and HDL mediated ³H-cholesterol efflux rates were significant correlated to NBD-cholesterol efflux rate in human macrophages (r=0.968, p<0.001).ConclusionNBD-cholesterol was a useful, sensitive and environmental protective probe for assay of human macrophage cholesterol efflux rate.

Abstract:Non high density lipoprotein cholesterol (non-HDLC) levels reflect concentration of total atherogenic cholesterol.Apolipoprotein B (ApoB) plasma levels reflect total atherogenic particle number.Recent studies have shown that both of them could be more accurate predictors of cardiovascular risk than traditional marker low density lipoprotein cholesterol.This review is to discuss the performance of these parameters in cardiovascular risk assessment and clinical practice.

Abstract:Interleukin-15 (IL-15), a cytokine discovered in recent years, is synthesized and secreted by a variety of cells and tissues, particularly showing high expression in skeletal muscle, and is considered as a novel myokines.IL-15 works in skeletal muscle and adipose tissue as a novel myokine, regulating the body’s metabolism of carbohydrate, fat, involving in the regulation of skeletal muscle atrophy, obesity and metabolic disorders.In particular, IL-15 also serves as an important inflammatory factor contributing to occurrence and development of atherosclerosis.It is of great significance to study the biological effects and pathophysiological significance of IL-15.

Abstract:Optical coherence tomography (OCT) which provides high-resolution images of the coronary arteries can allow us to demonstrate clearly culprit lesion morphologies about the types of plaque and find out the vulnerable plaque, to identify the extent of stent malapposition and assess the proportion of uncovered struts and guide the stents implantation. These years OCT has made a great progress.The article reviews the research status in this aspect.