Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction

Journal of Interventional Cardiology
Mayra GuerreroWilliam W O'Neill

Abstract

Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group ...Continue Reading

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Citations

Feb 4, 2012·Gene Therapy·K IshikawaY Kawase
Mar 23, 2011·Cardiovascular Revascularization Medicine : Including Molecular Interventions·Maythem SaeedAlastair Martin
Jul 7, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yun YangJianwu Dai
Oct 4, 2018·Current Gene Therapy·Cen YanYing-Mei Feng
Aug 1, 2020·Journal of Anesthesia·Shogo SuzukiKimitoshi Nishiwaki

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