The main objective of this grant is to minimize infarct expansion and to understand how left ventricular dilatation can be attenuated. The overall hypothesis of this proposal is that cellular and molecular interventions during infarct repair will improve post-infarct remodeling and thereby improve cardiac contractile function. By using an animal model, we will address the following specific aims: 1) to determine how remodeling is altered by skeletal muscle and fibroblast grafting 2) to determine if accelerating granulation tissue formation using growth factors i.e. VEGF and bFGF will alter remodeling 3) to determine if endothelial progenitor cell grafting can accelerate granulation tissue formation and alter remodeling. By engrafting skeletal muscle and fibroblast cells to the infarcted wall of rats, we will determine how they improve overall ventricular contractility. The remodeling process and its effect on ventricular function will be evaluated using echocardiography, left heart catheterization, morphometric measurements, and histology. In two separate experiments, we will accelerate granulation tissue formation. The first experiment will use VEGF and bFGF to create angiogenesis and limit infarct expansion in rat infarcts. Angiogenesis will be quantified using radioactive microspheres. The second will utilize the Tie2/LacZ mouse. Endothelial progenitor cells from these mice will be injected to the infarcted wall to create de-novo vessel formation, which will stain blue on histology.
| Minami, Elina; Laflamme, Michael A; Saffitz, Jeffrey E et al. (2005) Extracardiac progenitor cells repopulate most major cell types in the transplanted human heart. Circulation 112:2951-8 |
