Hypoxia-mediated release of peptide growth factors from neonatal pulmonary artery smooth muscle cells † 1453

Abstract

Hypoxia leads to neonatal pulmonary hypertension and vascular remodeling. We evaluated the hypoxia-induced release of basic Fibroblast Growth Factor(bFGF), Vascular Endothelial Growth Factor (VEGF)(Vascular Permeability Factor) and Endothelin-1(ET-1) from neonatal piglet pulmonary artery smooth muscle cells (SMC). Conditioned media (CM) from confluent hypoxic (1% O2) and normoxic (20% O2) SMC was analyzed for bFGF and ET-1 by ELISA, and for VEGF by Western blotting. The effect of the conditioned media on SMC proliferation in vitro was also measured. Our results indicate: 1) CM from hypoxic SMC increases proliferation of normoxic SMC, and this mitogenic effect is abolished by antibody to bFGF, but not to VEGF; 2) Hypoxia increases bFGF in CM despite equivalent amounts of bFGF in cell lysate; 3)Hypoxia increases VEGF release; 4) No release of ET-1 with hypoxia. These findings suggest that bFGF and VEGF may be involved in the smooth muscle proliferation (via bFGF), and the intimal proliferation and interstitial edema(VEGF) seen in the hypoxic pulmonary vasculature.Figure