Potent endothelial progenitor cell-conditioned media-related anti-apoptotic, cardiotrophic, and pro-angiogenic effects post-myocardial infarction are mediated by insulin-like growth factor-1

• Published in: European heart journal 2013-03, Vol.34 (10), p.782-789
• Main Authors: Hynes, Brian, Kumar, Arun H S, O'Sullivan, John, Klein Buneker, Chirlei, Leblond, Anne-Laure, Weiss, Sharon, Schmeckpeper, Jeffrey, Martin, Kenneth, Caplice, Noel M
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - physiology; Apoptosis - physiology; Biomarkers - metabolism; Cardiotonic Agents - pharmacology; Cell Survival; Culture Media, Conditioned - pharmacology; Endothelial Cells - physiology; Endothelial Cells - transplantation; Female; Heart Ventricles - pathology; Insulin-Like Growth Factor I - antagonists & inhibitors; Insulin-Like Growth Factor I - immunology; Insulin-Like Growth Factor I - pharmacology; Myocardial Contraction - physiology; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocytes, Cardiac - physiology; Neovascularization, Physiologic - physiology; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Stem Cell Transplantation - methods; Stem Cells - physiology; Sus scrofa; Ventricular Dysfunction, Left - pathology; Ventricular Dysfunction, Left - therapy
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehr435

We have previously reported the cardioprotective effects of endothelial progenitor cell (EPC)-conditioned media (CM) therapy post-myocardial infarction (MI). In the present study, we have determined the insulin-like growth factor-1 (IGF-1) contribution to EPC CM effects on cardiomyocyte survival, contractility, and angiogenesis in vivo. Conditioned media from porcine EPC were administered intracoronary in the presence and absence of specific neutralizing antibodies to IGF-1 or control IgG in a porcine model of MI. X-vivo (non-conditioned) medium was used as a control. Functional, histological, and biochemical parameters were evaluated at 24 h and 8-week post-therapy. Conditioned media therapy significantly abrogated infarct zone (IZ) apoptosis, hypocontractility, and impaired left ventricular (LV) relaxation observed in control infarcts acutely (24 h post-MI). At 8 weeks following treatment, CM therapy augmented LV contractility and relaxation, IZ angiogenesis and inhibited infarct size expansion, wall expansion, and wall thinning. All of these acute and chronic beneficial effects of CM therapy were vitiated by neutralizing antibodies to IGF-1 but not by control IgG. Moreover, the addition of neutralizing IGF-1 antibody to control medium had no effect on these structural or functional changes in the heart post-treatment. Insulin-like growth factor-1 within the EPC CM mediates potent acute myocardial repair and chronic remodelling effects post-MI. These findings may provide a rationale for comparative trials of specific growth factors vs. current progenitor cell strategies.