Abstract
Objective Endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) have been implicated in protection against myocardial ischemia injury. This study was designed to explore a new method of therapy for myocardial injury by eNOS gene transfection. Methods A rat model of myocardial infarction (MI) was established by left anterior descending (LAD) coronary artery ligation. eNOS gene in an adenovirus vector was delivered locally into the rat heart and hemodynamic parameters were examined after 3 weeks, Matrix metalloproteinase-2 and 9 (MMP-2, MMP-9) mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR), and the protein levels of eNOS, caspase-3, and transforming grouth factor β1 (TGF-β1) were determined by western blot assay. Results eNOS gene transfer significantly reduced cardiomyocyte apoptosis and improved cardiac function. In addition, eNOS significantly reduced the mRNA levels of MMP-2 and MMP-9. In the eNOS gene transfected group, the activation of caspase-3 and TGF-β1 were decreased. However, the protection was reversed by administration of the NOS inhibitor, N(ω)-nitro-l-arginine methyl ester (L-NAME). Conclusion These results demonstrate that the eNOS provides cardiac protection after myocardial infarction injury through inhibition of cardiac apoptosis and collagen deposition, and suppression of TGF-β1.
Highlights
Cardiac remodeling after myocardial infarction (MI) involves myocyte hypertrophy, chamber dilation, and interstitial fibrosis
To evaluate the apoptosis after MI, we examined the caspase-3 expression after Endothelial nitric oxide synthase (eNOS) gene delivery as shown in Fig. 4A and 4B
Cardiomyocyte-specific eNOS overexpression improved left ventricle (LV) performance and remodeling after infarction, suggesting that strategies to increase eNOSderived nitric oxide (NO) production might provide promising treatments to improve LV remodeling and function in the failing heart . [17,18,19,20] In the present study, we showed that the ventricular remodeling process after MI was associated with increased eNOS production from the non-infarcted myocardium and demonstrated that eNOS gene transfection attenuated the remodeling and preserved cardiac function in a rat model of MI
Summary
Cardiac remodeling after myocardial infarction (MI) involves myocyte hypertrophy, chamber dilation, and interstitial fibrosis. Alterations in both cardiomyocytes and collagen matrix lead to contractile dysfunction and contribute to the progression of ventricular enlargement and heart failure[1,2]. Endothelial nitric oxide synthase (eNOS) is a major source of nitric oxide (NO), which plays an important role in the pathophysiology of postinfarction ventricular remodeling and heart failure[3]. Inhibition of eNOS production results in impaired endothelium-dependent vasodilation and vascular endothelial growth factor (VEGF)-induced mobilization of endothelial progenitor cells. Some drugs that upregulate eNOS may be used for improving ventricular remodeling and function after MI[8]
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