Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPBAJGELMAN, Marcio C.SANTOS, Leonardo dosSILVA, Gustavo J. J.NAKAMUTA, JulianaSIRVENTE, Raquel A.CHAVES, MarcioKRIEGER, Jose EduardoSTRAUSS, Bryan E.2015-07-012015-07-012015VIROLOGY, v.476, p.106-114, 20150042-6822https://observatorio.fm.usp.br/handle/OPI/9322Here we present the application of our adeno-associated virus (AAV2) vector where transgene expression is driven by a synthetic, p53-responsive promoter, termed PG, used to supply human vascular endothelial growth factor-A(165) (VEGF-A). Thus, p53 is harnessed to promote the beneficial expression of VEGF-A encoded by the AAVPG vector, bypassing the negative effect of p53 on HIF-1 alpha which occurs during cardiac hypertrophy. Wistar rats were submitted to pressure overload induced by thoracic aorta coarctation (TAC) with or without concomitant gene therapy (intramuscular delivery in the left ventricle). After 12 weeks, rats receiving AAVPG-VEGF gene therapy were compared to those that did not, revealing significantly improved cardiac function under hemodynamic stress, lack of fibrosis and reversal of capillary rarefaction. With these functional assays, we have demonstrated that application of the AAVPG-VEGF vector under physiologic conditions known to stimulate p53 resulted in the preservation of cardiac performance.engrestrictedAccessCardiac hypertrophyp53VEGFAAVHIF1endothelial growth-factorangiotensin-converting enzymeheart-failuremyocardial-infarctionpressure-overloadgene-transferconscious dogsangiogenesisdysfunctionratsarticleCopyright ACADEMIC PRESS INC ELSEVIER SCIENCE10.1016/j.virol.2014.12.009Virology