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Objective To observe the phosphorylation levels of extracellular signal-regulated kinase 5 (ERK5) in acute myocardial infarction (AMI) patients and the effects of ERK5 selective inhibitor XMD8-92 on human platelet activation in vitro,and to explore its mechanism.Methods Western blot was applied to detect the phosphorylation levels of ERK5,Akt473 and Akt308 in AMI patients (n =34) and stable angina patients (n =33,control).The effects of different concentration of XMD8-92 on human platelet aggregation induced by collagen was tested by aggregometer in vitro.The release of ATP was measured simultaneously by luciferase detection.The effects of XMD8-92 on integrin aIIbβ3 were detected by platelet spreading on immobilized fibrinogen and clot retraction.The effects of XMD8-92 on phosphorylation levels of Akt473,Akt308 PTEN370 and ERK5 were detected by Western blot.Results The levels of phosphor-Akt473,Akt308 and phosphor-ERK5 were significantly higher in AMI patients than that in control group (P＜0.05).ERK5 inhibitor XMD8-92 diminished collagen-induced platelet aggregation,ATP secretion,the average area of platelet spreading on immobilized fibrinogen and the clot retraction extent.The levels of phosphor-Akt (Ser-473/Thr-308) and phosphor-PTEN (Ser370) were significantly down-regulated in the presence of XMD8-92.Conclusions ERK5 plays a role in platelet activation in AMI process.It regulates platelet activation by regulating PTEN and Akt phosphorylation.Its specific inhibitor is hoped to be new antithrombotic drug.
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Objective To investigate the impact of paced QRS duration (pQRSd) on heart function in patients with right ventricular apical pacing. Methods Seventy-six patients with Ⅲ° atrioventricular block received pacemaker treatment were enrolled and randomized into group A (pQRSd 0.05). At 24 months after implanting, LAD、LVEDD、LVESD of group B increased significantly compared with those of group A [LAD,( 44.5 ± 6.2) mm vs (41.6 ± 5.1) mm, LVEDD, (52.7 ± 9.3) mm vs (48.2 ± 7.5) mm, LVESD, (37.5 ± 5.6) mm vs (33.8 ± 4.9)mm, each P 0.05)between two groups during 24-month follow-up. Conclusion The prolonged paced QRS duration has a detrimental effect on long-term cardiac function during RVA pacing in patients with Ⅲ°atrioventricular block.
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We tried to construct and identify the recombinant replication-deficient adenovirus vector coding for human tissue factor pathway inhibitor 2 (hTFPI-2) gene by AdMax system in HEK293 cells. Firstly, we obtained hTFPI-2 gene from the recombinant plasmid pIRES2-EGFP-TFPI-2 by PCR using primers with restriction endonuclease site of EcoRI or SacI. After digesting the hTFPI-2 gene and plasmid PDC316-IRES-EGFP shuttle vector, we ligated them with T4 ligase and formed the recombinant shuttle vector PDC316-IRES-EGFP-hTFPI-2. It was confirmed that the ligation product was inserted the gene of hTFPI-2 correctly by sequencing. Then we took cotransfection of HEK293 cells with the recombinant shuttle vector and genomic plasmid pBHGloxdeltaE1,3Cre by liposome lipofectamine2000, and finished the package of recombinant adenovirus Ad-hTFPI-2. The results of the PCR test and restriction endonuclease digestion confirmed the successful construction of the recombinants Ad-hTFPI-2. Furthermore, we measured the titre of Ad-hTFPI-2 with the aid of green fluorescence protein expression after multiplication and purification. The titre was 0.931 x 10(12) pfu/ml. Finally, we infected U937 monocytes by purified Ad-hTFPI-2, and determined the infection efficiency and the TFPI-2's level and activity. The efficiency of Ad-hTFPI-2 infection in U937 cells was 89.33%. After infected by Ad-hTFPI-2, the TFPI-2's level in supernatant increased about 7 fold. Also the TFPI-2 in supernatant had activities of inhibiting trypsin and plasmin. The recombinant adenovirus with the hTFPI-2 gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in antiatherosclerosis.
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Humans , Adenoviridae , Genetics , Metabolism , Defective Viruses , Genetics , Metabolism , Genetic Vectors , Genetics , Glycoproteins , Genetics , Monocytes , Metabolism , Recombinant Proteins , Genetics , Transfection , U937 CellsABSTRACT
AIM:To observe the improvement in the endothelial function of patients with long-term use of Shexiang Baoxin Pill(Moschus,Ginseng extract,Calculus bovis,Cortex cinnamomi,Styrax,Venenum bufonis,and Borneolum Syntheticum)(SXBXP).METHODS:Eighty patients with CHD were randomly assigned into the SXBXP group and the control group.Two groups were controlled with the usual treatment.SXBXP 2 pills,po.tid.were taken in the SXBXP group and continued for at least 6 months.The ultrasound assessment of endothelial-dependent flow-mediated vasodilation(FMD)of the brachial artery was applied in the 3rd,6th and 18th and simultaneous determination of nirtogen oxides(NO),nitricoxide synthase(NOS),superoxide dismutase(SOD),endothelin(ET)was made.RESULTS:Follow-up checkups revealed that the level of FMD and SOD in the 3rd month,the level of NO,NOS and ET in the 6th month in SXBXP group were better than those in the control group at the significant level(P＜0.05).Patient keeping on taking SXBXP up to the 18th month,the obvious improvement in the level of FMD,NO,NOS and SOD was showed(P＜0.05).CONCLUSION:Administration of SXBXP could improve endothelial function in the CHD patients significantly.
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ObjectiveTo assess the relationship between the estimated glomerular filtration rate (eGFR) and the severity of coronary artery stenosis in elder people. MethodsSix hundred and fifty-seven patients who underwent selective coronary artery angiography were divided into 3 groups according to age: group Ⅰ (202 patients aged <60 years), group Ⅱ (181 patients aged from 60 to 69 years) and group Ⅲ (274 patients aged ≥70 years). According to the simplified MDRD equation,impaired renal function and severe renal dysfunction, respectively. Clinical features and the severity of coronary artery stenosis were compared among the 3 groups. ResultsThe level of average eGFR tended to he decreased with the narrowed coronary arteries. The difference of average eGFR between patients with muhivessel versus two-vessel coronary artery disease was of statistical significance in Group Ⅲ(P = 0. 035). After controlling for the effects of smoking, hypertension, dyslipidemia,aging, and diabetes, the Gensini score which reflected the severity of coronary artery stenosis was negatively correlated with the level of eGFR (r =-0. 110, P = 0. 005). ConclusionsIt suggests that the eGFR decrease is associated with the severity of coronary artery stenosis, and there is a linear correlation between eGFR and Gensini score in elder people, eGFR can be used to evaluate the severity of coronary artery disease and prognosis.
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BACKGROUND: Results from clinical trials suggested that clopidogrel and ticlopidine had side effects of granulopenia, and aspirin could inhibit endothelial progenitor cell proliferation. There is no report of effects of these drugs on human bone marrow mesenchymal stem cells (hBMSCs) in stem cell transplantation. OBJECTIVE: To investigate the effects of antiplatelet drugs including clopidogrel, ticlopidine and aspirin on hBMSC proliferation and secretion. DESIGN, TIME AND SETTING: The cytology in vitro observation was performed at the Laboratory of Toxicology, Shanghai Municipal Center for Disease Control and Prevention from March to December 2006.MATERIALS: The second passage of hBMSCs was kindly donated from Shanghai Tissue Engineering Research & Development Center, Shanghai Ninth People's Hospital. Clopidogrel (Lot number J20040006) and ticlopidine (Lot number H19980186) were obtained from Hangzhou Sanofi-Synthelabo Minsheng Pharmaceutical CO., Ltd. Aspirin (Lot number 20050059) was obtained from Bayer Vital GmbH. METHODS: The standard culture medium consisted of DMEM-LG, 10% heat-inactivated FBS, 100 U/mL penicillin and 100 μg/mL streptomycin. After being cultured in vitro expanded out to passage 6, hBMSCs were treated with antiplatelet drugs of different concentrations and compared with control group. MAIN OUTCOME MEASURES: Cell proliferation was assessed by 3- (4, 5-dimethylthiazol -2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay, level of vascular endothelial growth factor (VEGF) of culture medium was detected by enzyme-linked immunoadsordent assay (ELISA), and surface antigens of hBMSCs were analyzed by the flow cytometry. RESULTS: A570 values of hBMSCs treated by clopidogrel or ticlopidine of 0.02,0.1,0.4,2,10,40 μmol/L were higher than control group (P < 0.01), while A570 values of aspirin group of 60, 600, 2 000 μmol/L were lower than control group(P < 0.05). Antiplatelet drugs had no obvious effect on cell surface antigens(CD34, CD105, CD106)expressed by hBMSCs. Treated by high dose clopidogrel or ticlopidine (40 μmol/L), VEGF level from hMSCs was lower than that of control group(P < 0.01), but VEGF level of low dose (0.02 μmol/L) ticlopidine group was higher than control group(P < 0.01), and there was no significantly difference of VEGF level among low dose clopidogrel group (0.02 μmol/L), aspirin group (5, 2 000 μmol/L), and control group(P > 0.05). CONCLUSION: Clopidogrel and ticlopidine improve proliferation of hBMSCs, but aspirin inhibits proliferation of hBMSCs. High dose of clopidogrel and ticlopidine suppress VEGF secretion of hBMSCs, while low dose of ticlopidine promote it. Antiplatelet drugs have no obvious effect on hBMSCs differentiation.
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Objective To compare the effects of clopidogrel and ticlopidine in combination with aspirin in preventing direct coronary stenting complication in patients with acute myocardial infarction.Methods The clinical data of 74 cases with ST-segment elevation myocardial infarction were retrospectively analysed. The patients were divided into two groups. Before direct coronary stenting, clopidogrel,300mg loading dose then 75mg once daily or ticlopidine 250mg twice daily in addition to aspirin 100mg once daily were given to two groups respectively. Hemorrhage, neutropenia, thrombocytopenia were observed during 4 weeks. The frequency of clinical cardiovascular events (including cardiac mortality, myocardial re-infarction, need for revascularization) were followed up at 6 months. Results The incidence of major cardiac events in clopidogrel group was less than ticlopidine group ( 21.1% with Clopidogrel and 44.4% with Ticlopidine,P= 0.031). The incidence of light hemorrhage patents individually were 6(15.8%) vs 14(38.9%). The mean number of neutrophile white celll individually were 5.8 ?1.7 vs 4.2 ?3.6 (?10 9/L). The platelet count were 130.3 ?42.1 vs 89.2 ?53.3(?10 9/L), P
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Objective To study the effect of Depside Salt from Salvia Miltiorrhiza on angina pectoris and platelet function.Methods The study group was comprised of 56 patients with stable angina,who were randomly divided into the high-dosage Depside Salt from Salvia Miltiorrhiza group,the low-dosage Depside Salt from Salvia Miltiorrhiza group and the Danshen control group. Before and after the 14-day treatment,the clinical symptom and serum level of PAG, P-selectin were measured,and exercise electrocardiography was performed. Results After treatment with Depside Salt from Salvia Miltiorrhiza,the symptom of angina pectoris was alleviated and exercise ECG was improved,while no significant difference was found compared with control group.Serum PAG and P-selectin were decreased after treatment with Depside Salt from Salvia Miltiorrhiza ,and significantly more than Danshen.Conclusion Depside Salt from Salvia Miltiorrhiza injection can remarkably inhibite the aggregation and activation of platelet,and is effective for angina pectoris.
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Objection To compare the efficacy and tolerance of perioperative intravenous Metoprolol or calcium iron antagonist injection on patients with cardiac complications which undergoing noncardiac surgery. Method The clinical data of 135 patients who underwent noncardiac surgery from March 2003 to May 2004 was analyzed. According to the different drugs used to treat the perioperative cardiac complications (tachycardia arrhythmia, hypertension and myocardium ischemia), patients were allocated to metoprolol group (87 cases) and calcium antagonist group (48 cases, including Verapamil 21 patients and Diltiazem 27 patients). The effects of the therapy on heart rate and blood ressure control and ischemia relieving were compared between two groups. Results There is no significant difference at baseline data between two groups. Compared with calcium antagonist, intravenous metoprolol could more reduce heart and relieve myocardium ischemia quickly. The effect of blood pressure controlling was more significant in calcium antagonist group than in metoprolol group. The incidence of side-effects events was lower in metoprolol ( 8.0%) than in calcium antagonist group (22.9%).Conclusions Intravenous metoprolol injection is effective and safe in treating perioperative cardiac complications in patients with noncardias surgery.
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OBJECTIVE: To study the effect of Zhenju Jiangya Tablet (ZJ) on the injured endothelial cells and endothelium-dependent relaxation function of hyperlipidemia rabbits. METHODS: Male New Zealand rabbits were randomized into four groups: control group, hyperlipidemia group, ZJ group and sivastatin group. The endothelium-dependent relaxation function was evaluated by APV using intravascular Doppler, and the morphology of endothelial cells was detected by light microscopy and electron microscopy, and nitric oxide synthase was evaluated. RESULTS: ZJ reduced the lesions of hyperlipidemia vessels, and the APV after Ach injection of each group was (1.14+/-0.26), (1.74+/-0.59), (1.22+/-0.37) and (1.17+/-0.41) respectively. The eNOS of each group was (4.21+/-0.37), (1.43+/-0.88), (3.95+/-0.67) and (4.08+/-0.46) nmol x min(-1) x g(-1) respectively. CONCLUSION: ZJ can improve the abnormality of endothelial cells and endothelium-dependent relaxation function of hyperlipidemia.
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0.05) after SVT episode. Compared to the SVT group and basic status, the extraction ration of glucose and oxygen of CAD patients obviously increased( P
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Until now, although the molecule of EDHF has not been cloned, some characteristics of EDHF has been clarified by scientists. It is different from NO and prostacyclin, and it is considered to play an important role in the regulation of vascular tone by stimulating the channels of K + and Ca 2+ .
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Objective To compare the long term outcomes of delayed or primary percutaneous transluminal coronary intervention(PCI) with concervative drug therapy for acute myocardial infarction(AMI).Methods The data of 276 patients with AMI hospitalized during January 1996 to October 2003 were analyzed retrospectively.The patients were divided into three groups including: primary PCI group(75 cases underwent primary PCI within 12 hours of symptom onset),delayed PCI group(73 cases underwent delayed PCI after 24 hours symptom onset) and conservative drug therapy group(128 cases without PCI treatment).Major adverse cardiac events(MACE) were recorded during the follow-up period(mean 4.3?2.7 years).Echocardiography was carried out and long-term mortality rate was recorded during follow-up.Results The Baseline characteristics of the three groups were similar except elevation in ST segment and in-hospital duration which were significantly different in the primary PCI group.The percentage of follow-up completion was 89.5%(247/276).The in-hospital mortality of the conservative therapy group was higher than both PCI groups.The LVEF of the delayed PCI group,primary PCI group and the conservation therapy group were 57.4%?3.4%,59.3%?7.5% and 54.7%?4.1% respectively.There was 1 deceased case in both the delayed and primary PCI group but 14 cases in the conservative group.There was no significant difference between the two PCI groups in terms of combined end point of death and clinical events different.Conclusion Compared with conservative drug therapy,delayed PCI can further improve the long-term prognosis of STEMI patients.
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0.05). Conclusion Combined inplantation of different types of DES is safe and does not increase the incidence of MACE.
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Objective: To investigate the effect of Shexiangbaoxin Pills on morphosis and function of left ventricle after myocardial infarction in rat. Methods: The rat myocardial infarction models induced by ligaturing coronary artery were randomly divided into the myocardial infarction control group, Shexiangbaoxin Pill group and captopril group. The hemodynamic parameters and cardiac functions in 2 or 6 weeks after treatment were determined. Meantime, the morphological parameters of left ventrile (left cardiac chamber size, attenuation proportion of ventricular wall of infarction area, and expansion index of left ventrile), were studied. Results: Shexiangbaoxin Pills could reduce the distention of left ventrile and expansion of infarction area of rat in 6 weeks after infarction. It could obviously improve the contraction function of left ventrile after myocardial infarction. Conclusion: Shexiangbaoxin Pills can improve left ventricular reconstitution after myocardial infarction.
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AIM: We observed the expression of KDR/Flk1 in post-myocardiac ischemia(MI) SD rats in order to explain the effect of captopril and its relationship with myocardium angiogenesis after long-term administration.METHODS: The MI model was made by LAD ligation.Captopril was administered for 6 weeks.Immuohistological method and FQ-PCR were used to test the myocardium KDR/Flk-1 expression.RESULTS: In captopril group,no inhibitory effect was observed in myocardium factor VIII expression,but KDR/Flk-1 decreased.The copies of KDR/Flk-1 mRNA reduced dramatically when compared to control group,false-operation and normal group(P0.05).CONCLUSION: ACEI down-regulates KDR/Flk-1 and its mRNA expression in ischemic rat myocardium after long-term administration of captopril,but does not inhibit angiogenesis.So we suspect that some other pathways exist,which can not affect by ACEI,or that ACEI just reduces abnormal angiogenesis.