Coinjection of AAV vectors expressing VEGF and Ang1 improved cardiac perfusion and function in a porcine myocardial infarction model by inducing angiogenesis and reducing apoptosis.
Does coexpression of VEGF and Ang1 improve cardiac function and perfusion in a porcine model of myocardial infarction?
Cardiac-specific and hypoxia-induced coexpression of VEGF and Ang1 improves perfusion and function in a porcine MI model by inducing angiogenesis and cardiomyocyte proliferation while reducing apoptosis.
VEGF and angiopoietin-1 (Ang1) are two major angiogenic factors being investigated for the treatment of myocardial infarction (MI). Targeting VEGF and Ang1 expression in the ischemic myocardium can increase their local therapeutic effects and reduce possible adverse effects. Adeno-associated viral vectors (AAVs) expressing cardiac-specific and hypoxia-inducible VEGF AAV-myosin light chain-2v (MLC)VEGF and Ang1 (AAV-MLCAng1) were coinjected (VEGF/Ang1 group) into six different sites of the porcine myocardium at the peri-infarct zone immediately after ligating the left descending coronary artery. An identical dose of AAV-Cytomegalovirus (CMV)LacZ or saline was injected into control animals. AAV genomes were detected in the liver in addition to the heart. RT-PCR, Western blotting, and ELISA analyses showed that VEGF and Ang1 were predominantly expressed in the myocardium in the infarct core and border of the infarct heart. Gated single-photon emission computed tomography analyses showed that the VEGF/Ang1 group had better cardiac function and myocardial perfusion at 8 wk than at 2 wk after vector injection. Compared with the saline and LacZ controls, the VEGF/Ang1 group expressed higher phosphorylated Akt and Bcl-xL, less Caspase-3 and Bad, and had higher vascular density, more proliferating cardiomyocytes, and less apoptotic cells in the infarct and peri-infarct zones. Thus, cardiac-specific and hypoxia-induced coexpression of VEGF and Ang1 improves the perfusion and function of porcine MI heart through the induction of angiogenesis and cardiomyocyte proliferation, activation of prosurvival pathways, and reduction of cell apoptosis.
Tao et al. (Tue,) conducted a other in Myocardial infarction. AAV-MLCVEGF and AAV-MLCAng1 coinjection vs. AAV-CMVLacZ or saline was evaluated on Cardiac function, myocardial perfusion, angiogenesis, cardiomyocyte proliferation, and apoptosis. Coinjection of AAV vectors expressing VEGF and Ang1 improved cardiac perfusion and function in a porcine myocardial infarction model by inducing angiogenesis and reducing apoptosis.
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