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Objective To investigate the relationship between matrix metalloproteinase-3 (MMP-3) gene promoter polymorphisms 5A/6A and the restenosis after percutaneous coronary intervention (PCI). Methods A total of 437 patients with PCI were selected in this study. Patients were divided into mutant genotype group (5A/5A+5A/6A, n=136) and wild genotype group (6A/6A, n=301) according to MMP-3 polymorphism. The angiography and clinic data were collected before and after coronary angiography in two groups of patients. The serum level MMP-3 and genotype analysis were compared be-tween two groups. Results There was no significant difference in the restenosis rate between two groups (42.2%vs 33.1%, P>0.05). The restenosis degree was significantly higher in wild genotype group than that in mutant genotype group (56.28%± 11.10%vs 36.00%±10.17%, P＜0.01). There was no significant difference in the serum level of MMP-3 between two groups (13.38μg/L ± 3.00μg/L vs 12.33μg/L ± 2.96μg/L, P>0.05). There was a higher restenosis rate in patients carrying 6A al-lele than that of patients carrying 5A allele (P＜0.05). Carrying wild genotypes are risk factors for restenosis after PCI. Con-clusion Patients carrying 6A allele have significantly higher risk of resteonsis than patients carrying 5A allele.
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<p><b>OBJECTIVE</b>To investigate cholesteryl ester transfer protein (CETP) gene polymorphism -629C/A among Han Chinese patients with coronary heart disease (CHD) in Tianjin region, and to assess the influence of genetic factors on therapeutic effect of atorvastatin and clinical outcome in order to provide a pharmacogenomic basis for personalized treatment.</p><p><b>METHODS</b>From October 2010 to July 2011, 232 patients with angiographically confirmed CHD were recruited. Polymorphism of position -629 of CETP gene promoter was determined with polymerase chain reaction - restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP was determined with enzyme-linked immunosorbent assay (ELISA). Lipid level in all patients was determined at baseline and after 12 months of treatment with 20 mg/d atorvastatin. Clinical follow-up was carried out for more than a year (12-23 months). Major adverse cardiac events including death, non-fatal infarction, revascularization and stroke (MACE) were recorded. A Kaplan-Meier log-rank test was used to compare MACE-free survival for individuals with various genotypes.</p><p><b>RESULTS</b>The frequency of -629A allele was 0.408. Compared with CC or CA genotypes, individuals with AA genotype had lower CETP levels and higher high-density lipoprotein cholesterol (HDL-C) levels, albeit without statistical significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282, respectively). There also appeared to be a negative correlation between serum HDL-C and CETP levels, though no statistical significance was detected (r = -0.151, P = 0.081). After 12 months atorvastatin therapy, individuals with CC genotype had greater reduction of low-density lipoprotein cholesterol (LDL-C), reduced LP(a) and elevated HDL-C compared with CA or AA genotypes. LDL-C level has decreased by 35.41% in CC homozygotes, 18.84% in CA heterozygotes and 8.15% in AA homozygotes (P = 0.001). HDL-C level has increased by 14.37% in CC homozygotes, 10.48% in CA heterozygotes and 6.64% in AA homozygotes, respectively. However, above changes did not reach statistical significance (P = 0.470). The incidence of MACE after a mean follow-up of (18.66 ± 5.99) months was 7.76%, which included 2 (0.86%) deaths, 5 (2.16%) non-fatal infarctions, 9 (3.88%) revascularizations and 2 (0.86%) strokes. The cumulative MACE-free survival rates were 92.4%, 85.3% and 65.0% for CC, CA and AA genotypes, respectively (Log-rank P = 0.444).</p><p><b>CONCLUSION</b>Our results suggested that AA variant for the -629A allele of CETP gene had higher HDL-C levels and reduced CETP levels, though patients with CC genotype appeared to have better benefited from statin therapy with reduction in LDL-C and LP(a) levels. Long-term clinical prognosis was however not affected by the 3 genotypes.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Atorvastatin , Cholesterol Ester Transfer Proteins , Blood , Genetics , Cholesterol, HDL , Blood , Cholesterol, LDL , Blood , Coronary Artery Disease , Blood , Drug Therapy , Genetics , Heptanoic Acids , Therapeutic Uses , Mutation, Missense , Polymorphism, Single Nucleotide , Pyrroles , Therapeutic Uses , Treatment OutcomeABSTRACT
BACKGROUND: Previous studies suggest that vascular endothelial growth factor 121 may be an optimal target gene for thetreatment of acute myocardial infarction.OBJECTIVE: To investigate effect of direct myocardial injection of adenovirus recombinant human vascular endothelial growthfactor 121 gene (Ad-hVEGF121) on myocardial infracted rat heart structure, function and angiogenesis.METHODS: Totally 78 male SD rats were randomly divided into the sham-surgery (n=18), acute myocardial infarction (n=24),Ad-VEGF121 (n=19) and normal saline (n=17) groups. Among them, left anterior descending coronary arteries of the latter threegroups were ligated to prepare acute myocardial infarction models and rats were randomly selected to receive Ad-hVEGF12 ornormal saline via three points in the cardiac muscle at the 10-15 minutes after ligation. The chest was exposed without ligation inthe sham-surgery group.RESULTS AND CONCLUSION: At 2 weeks after injection, cardiac ultrasound showed that, compared with the sham-surgerygroup, the number of new capillaries, body weight and left ventricular mass / body weight of the acute myocardial infarction,Ad-hVEGF121 and normal saline groups were obviously increased (P < 0.05 or P < 0.01), especially those received transfectedrAd-hVEGF12, had higher density of blood capillaries than those of the normal saline and acute myocardial infarction groups.However, there were no obviously differences between each group in infarct size, cardiac structure or functions. The directmyocardial injection of Ad-VEGF121 can significantly promote the formation of new blood vessels within the myocardium.
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Objective:To investigate the effect of chronic alcohol consumption on both left ventricular myocardial collagen and diastolic function in rats,and their relationship thereof.Methods:Twenty-four male Wistar rats were randomly divided into 2 groups:control group(n=12)and ethanol group(n=12).The changes in cardiac diastolic function were evaluated by echocardiography and tissue Doppler imaging(TDI).The value of myocardial hydroxyproline content was determined by hydroxyproline reagent kit.The expressions of collagen Ⅰ and collagen Ⅲ mRNA were detected by RT-PCR analysis.Results:It was found that mitral E and mitral annulus Ea were decreased,mitral annulus Aa was increased,and isovolumic relaxation time(IVRT)was prolonged in the ethanol group compared with those in control group(P＜0.05).The value of Ea/Aa ratio was greater than 1 in control group and less than 1 in ethanol group(P＜0.01).It was found that myocardial hydroxyproline content,collagen Ⅰ,collagen Ⅲ mRNA expression and their ratio significantly increased in ethanol group compared with those in the control group(P＜0.01).There was positive correlation between hydroxyproline content,collagen Ⅰ,collagen Ⅲ mRNA expression,and collagen Ⅰ /collagen Ⅲ mRNA ratio with IVRT(P＜0.05),and negative correlation between hydroxyproline content,collagen Ⅰ,collagen Ⅲ mRNA expression,and collagen Ⅰ /collagen Ⅲ mRNA ratio with the Ea/Aa ratio(P＜0.01).Conclusion:Chronic ethanol consumption can induce increase in left ventricular myocardial collagen synthesis and impairment in diastolic function in rats.Left ventricular diastolic dysfunction correlates with increase in myocardial collagen synthesis positively.
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Objective To examine the expression of angiotensin Ⅱ (Ang Ⅱ) receptor subtypes in human left and right atrial tissue in atrial fibrillation underlying rheumatic heart disease. Methods Atrial tissue samples were obtained from 39 patients with rheumatic heart disease, 25 with atrial fibrillation(AF) and 14 with sinus rhythm(SR) during open heart surgery. AT1 and AT2 mRNA levels were measured with semi-quantitative reverse transcription polymerase chain reaction techniques. AT1 and AT2 protein levels were measured with immunohistochemical techniques. Results Compared with that of the SR group, left atrial inner diameter was significantly increased in the patients of the AF group. The AT1 mRNA and protein levels in the LA significantly increased in patients with AF compared with those in patients with SR (P < 0. 05), whereas AT2 mRNA and protein were not significantly altered. Investigations of Ang Ⅱ receptor subtypes' mRNA and protein levels in the RA did not exhibit any significant changes either in AT1 or AT2 in patients with AF and SR. Conclusions AF is associated with an up-regulation of AT1 in LA, but does not appear to influence the AT2 expression. This may indicate a possible pathophysiologie role for renin-angiotensin system in the development of AF. The series of effects mediated by ATI activation may be one of the molecular mechanisms involved in the process of atrial remodeling.
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Objective To investigate the association of monocyte chemoattractant protein-1 (MCP-1) promoter -2518A/G gene polymorphism with coronary lesions and in stent restenosis in Tianjin Chinese population. Methods Two hundred and seventy six patients who underwent percutaneous coronary intervention (PCI) and coronary angiography during follow-up were enrolled in the study. The MCP-1 gene promoter polymorphism at position -2518 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The frequencies of three genotypes of MCP-1-2518A/G polymorphism were 21.0% AA, 34. 1% GG,44.9% AG, respectively. There were no statistical differences in the number and the mean degree of stenosis vessels before PCI among 3 genotype groups (all P＞0.05). 113 cases developed in-stent restenosis and 163 cases were free from restenosis. In restenosis group, the AA, AG and GG genotype frequencies were 23.9%, 40.7%, 35.4%, against 19.0%, 47.9% and 33.1% in nonrestenosis group (P = 0. 446) . The frequencies of -2518A and G allele were 44.2%, 55.8% in restenosis group versus 42.9%, 57. 1% in non-restenosis group(P=0. 761). Conclusions The polymorphism of MCP-1-2518 A/G gene may be associated with neither atherosclerosis nor the in-stent restenosis.