Abstract
Recombinant adeno-associated virus (rAAV)-based gene therapy represents a promising approach for the treatment of heart diseases. It has been shown that growth hormone (GH) exerts a favorable effect on cardiovascular function in clinical and animal studies. This study explores a chronic stage after myocardial infarction and the potential therapeutic effects of delivering a human GH gene by rAAV following coronary artery ligation in Sprague–Dawley rats. rAAV vectors stably transduced heart muscle for up to 22 weeks after myocardial infarction (MI). Overexpression of GH via rAAV vectors significantly improved not only cardiac function but also LV pathologic remodeling was attenuated post-MI compared to the control rAAV-lacZ injected group. rAAV-mediated expression of GH also resulted in a significant induction of several angiogenic genes such as eNOS, VEGF and bFGF in rat hearts. Immunohistochemistry revealed an increase in capillary density and proliferation of cells and a decrease in the number of TUNEL-positive cardiomyocytes in the rAAV-GH group. Based on these data, we conclude that rAAV-mediated GH delivery can render a long-term transduction in the infarcted heart and improve cardiac function through promoting angiogenesis and proliferation of cells and protecting cardiomyocytes from ischemia-induced apoptosis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
