Preservation of cardiac function in left ventricle cardiac hypertrophy using an AAV vector which provides VEGF-A expression in response to p53

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art_BAJGELMAN_Preservation_of_cardiac_function_in_left_ventricle_cardiac_2015.PDF (1.09 MB)
Citações na Scopus
15
Tipo de produção
article
Data de publicação
2015
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ACADEMIC PRESS INC ELSEVIER SCIENCE
Autores
BAJGELMAN, Marcio C.
SANTOS, Leonardo dos
SILVA, Gustavo J. J.
SIRVENTE, Raquel A.
CHAVES, Marcio
Citação
VIROLOGY, v.476, p.106-114, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Here 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.
Palavras-chave
Cardiac hypertrophy, p53, VEGF, AAV, HIF1
URI
https://observatorio.fm.usp.br/handle/OPI/9322
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03