Premium
Angiotensin‐(1‐7) improves engraftment and reparative potential of cardiac progenitor cells in a rat model of myocardial infarction (1180.17)
Author(s) -
Qi Yanfei,
Bruce Erin,
Shenoy Vinayak,
Vohra Ravneet,
ColeJeffrey Colleen,
Abbatematteo Joseph,
Zingler Michael,
Walter Glenn,
Pepine Carl,
Katovich Michael,
Raizada Mohan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1180.17
Subject(s) - angiotensin ii , myocardial infarction , medicine , contractility , cardiac function curve , progenitor cell , cardiology , ejection fraction , endocrinology , heart failure , renin–angiotensin system , chemistry , stem cell , biology , receptor , microbiology and biotechnology , blood pressure
Angiotensin‐(1‐7) [Ang‐(1‐7)] has been shown to produce a multitude of effects on endothelial progenitor cells, implicating a role for this peptide in vascular repair. Our studies have shown that Ang‐(1‐7) enhanced proliferative and tube‐forming abilities of cardiac progenitor cells (CPCs), prevented hypoxia‐induced inhibition of migration and protected them against H 2 O 2 ‐induced cell death. These observations have led us to hypothesize that Ang‐(1‐7) would enhance CPCs reparative capacity and improve cardiac function in a rat model of myocardial infarction (MI). CPCs alone or CPCs overexpressing Ang‐(1‐7) (4 × 10 6 ) were intravenously injected into MI rats and cardiac functions were examined to test this hypothesis. Rats with MI exhibited reduced ejection fraction (EF, 33.0% ± 1.5 vs 77.0% ± 3.9 for control), increased left ventricular hypertrophy [VH, 3.6 ± 0.1 vs 2.7 ± 0.1 for control, (g/kg)], and decreased contractility (dP/dt max , 7235 ± 271.9 vs 10394 ± 326.3 for control, mmHg/sec). Compared with untreated MI rats, administration of CPCs alone restored EF by 42%, decreased VH by 11%, and improved dP/dt max by 23%; remarkably, treatment with CPCs overexpressing Ang‐(1‐7) improved EF by 79%, decreased VH by 17%, and attenuated the reduction in dP/dt max by 42%. Furthermore, Ang‐(1‐7) enhanced the engraftment of CPCs by two‐fold in the peri‐infarct myocardium. These observations demonstrate that Ang‐(1‐7) potentiates functionality and improves engraftment of transplanted CPCs to protect against MI. Thus, genetic modification of CPCs with Ang‐(1‐7) could be a valuable therapeutic strategy for ischemic heart diseases.