Endothelial Nitric Oxide Synthase Gene In Rat Ventricular Myocardial Infarction Remodeling

Objective To analyze the dynamic changes of transforming growthfactor(TGF)-β1 and p38 mitogen-activated protein kinase(p38MAPK) and pp38MAPKin the ventricular remodeling process of rat after myocardia l infarction(MI) and revea l the roles of them in this process.Methods Rats model of myocardia l infarction were performed by left coronaryligation and sham operated rats were designated to control groups. Hemod ynamicchanges were examined at 1th, 7th, 14th, 21th day; infarcted areas were observed byhematoxylin-eosin staining; the protein levels of TGF-β1, p38MAPK and the pp38MAPKwere determined by western blot analysis.Results The hemod ynamic differences were remarkable between the MI groups andsham groups. The fibrosis of cardiac tissue was gradua lly progressed. The proteinlevels of TGF-β1 were increased step by step and the expressions of p38MAPKprotein were uncha nged after MI , but the p-p38MAPK of MI groups reached theirpeaks at the 7th day after MI and then reduced at correspond ing time.Conclusion TGF-β1 was increased at correspond ing time after MI , which ma yactivate the phosphorylation of p38MAPK. TGF-β1 participated in the ventricularremodeling of MI, at least, which is one of the most possible pathogenesis. Objective To evaluate the protection of eNOS gene on ventricularremodeling after acute myocardia l infarction of rat.Methods Rats model of myocardia l infarction were performed by left coronaryligation, then eNOS gene in an adenovirus vector, or the same amount of norma lsaline, or empty adenovirus vector was delivered loca lly into rat heart nearby theinfarcted areas. All the myocardial infarcted rats were executed after 3 weeks. Cardiacfunction was measured by POWERlab system; cardiomyocyte apoptosis was detectedby terminal deoxynucleotidy transferase-med iated dUTP nick end labeling(TUNEL);matrix meta lloproteinase-2, 9(MMP-2, MMP-9) were measured by RT-PCR; caspase-3, eNOS, and transforming growth factor(TGF) -β1 were determined by western blotanalysis.Results In the group of transfection of eNOS gene, apoptotic cardiomyocyteswere remarkablely lower in the area of myocardial infarction nearby, the mRNA leverof MMP-2 and 9 were lower compared to the other groups. In this group, theactivation of eNOS was dramatica lly increased, however, caspase-3 and TGF-β1 weredecreased.Conclusion These results demonstrate that eNOS gene provides some treatment byinhibiting apoptosis and extracellula r matrix remodeling, improving cardiac function ,and attenuating ventricular remodeling.