Abstract P199: Placental Growth Factor Regulates Cardiac Adaptation and Hypertrophy Through a Paracrine Mechanism
Objective. Paracrine growth factor-mediated crosstalk between cardiac myocytes and non-myocytes in the heart is critical for programming adaptive cardiac hypertrophy in which myocyte size, capillary density, and the extracellular matrix function coordinately. Here we examined the role that placental growth factor (PGF) plays in the heart as a paracrine regulator of myocyte to non-myocyte communication and its influence on cardiac adaptation to stress stimulation using overexpressing and PGF knockout mice.
Methods and results. We identified PGF as a secreted factor that is predominantly produced in the heart during pressure overload. We studied mice with conditional post-natal PGF overexpression (PGF DTG). While these mice did not have a baseline phenotype, except increased fibrosis with aging, they responded to pressure overload stimulation induced by transverse aortic constriction (TAC) by an increase in hypertrophy (VW/BW (mg/g): 6.6 ± 0.2 for PGF DTG versus 5.6 ± 0.2 for controls; n ≥ 6 per group; p<0.01), capillary density (vessels/myocyte: 1.6 ± 0.05 for PGF DTG versus 1.4 ± 0.03 for controls; n ≥ 7 per group; p<0.01) and fibrosis. Despite a mild increase in fibrosis, cardiac function remained intact even after 12 weeks of pressure overload. On the other hand, PGF knockout mice (Pgf-/-) succumbed to heart failure within a week of pressure overload (fractional shortening (%): 20.2 ± 2.3 for Pgf-/- versus 30.4 ± 1.1 for controls; n ≥ 7 per group; p<0.01). These hearts displayed dilation and capillary rarefaction (vessels/myocyte: 1 ± 0.05 for Pgf-/- versus 1.2 ± 0.04 for controls; n ≥ 7 per group; p<0.01). Mechanistically we show that PGF has no direct effect on the cardiomyocytes but works through its direct actions on endothelial cells and fibroblasts by inducing capillary growth and fibroblasts proliferation.
Conclusion. PGF is a secreted factor that supports hypertrophy and cardiac function during pressure overload by affecting endothelial cells and fibroblasts.
- © 2011 by American Heart Association, Inc.