PGF role in regulating cardiac remodeling

Project: Research

Investigators

  • Federica Accornero (PI)

Description

Maintenance of cardiac function depends on a correct balance between the size of cardiomyocytes, the number of cardiac vessels and cardiac fibroblast activity. During the adaptive phase of cardiac hypertrophy endothelial cells and cardiac fibroblasts support cardioprotection and cardiomyocyte hypertrophy, at least in part by producing paracrine factors. Although it is clear that secreted molecules from non-myocytes contribute to the paracrine melieu associated with heart remodeling or increased workload, the identity of these factors remain elusive. We identified Placental growth factor (PGF) as a prominent factor that will be investigated here. PGF is a member of vascular endothelial growth factor (VEGF) family and is a ligand of the VEGF receptor 1 (Flt1). Our preliminary results show that PGF is an inducible secreted factor predominantly expressed by non-myocytes during hypertrophy, and that inducible cardiac overexpression of PGF results in an enhanced hypertrophic response to pressure overload, enhanced capillary growth and enhanced fibrosis. However we did not observe an independent effect of PGF on myocyte hypertrophy in a tissue culture assay. Therefore PGF is hypothesized to support compensated hypertrophy through activation of fibroblasts and endothelial cells. To address the hypothesis that PGF is protective for the heart, the progression from compensatory hypertrophy to heart failure will be analyzed in PGF transgenic mice subjected to pressure overload. Pgf null mice will be examined to study the requirement for PGF during hypertrophy and the response of endothelial cells and fibroblasts to pressure overload in the absence of PGF. Finally the ability of PGF to directly stimulate cardiac fibroblasts proliferation and secretion of pro-hypertrophic factors in vitro will be examined.
Award amount$88,000.00
Award date07/01/2011
Program typePostdoctoral Fellowship
Award ID11POST7530035
Effective start/end date07/01/201106/30/2013
StatusFinished