MODULATION OF INSULIN-LIKE-GROWTH-FACTOR (IGF) AND IGF BINDING-PROTEIN BIOSYNTHESIS BY HYPOXIA IN CULTURED VASCULAR ENDOTHELIAL-CELLS

Endothelial cells (EC) are hypoxia-tolerant and their capacity to prol iferate in low oxygen tension is essential to maintain vascular endoth elium integrity. The present study addresses whether hypoxia alters th e expression oi insulin-like growth factor (IGF) and IGF binding prote in (IGFBP) genes in bovine aortic EC (BAEC) and bovine pulmonary arter y EC (BPAEC). EC were cultured in normoxic (21%) conditions and expose d to 0% oxygen for 24, 48, or 72 h; some cells were reoxygenated by ex posure to 21% oxygen for 24 or 48 h following hypoxia. IGF-I peptide a nd mRNA levels were very low in both cell types, and decreased further with exposure to hypoxia. Ligand blotting showed that both cell types synthesized 24 kDa (IGFBP-4), 30 kDa (IGFBP-5 and/or IGFBP-6), 43 kDa and 48 kDa IGFBPs (IGFBP-3 glycosylation variants). IGFBP-4 was the p redominant IGFBP expressed by both cell types and did not change with exposure to hypoxia. Hypoxia caused a significant increase in IGFBP-3 secretion in BPAEC but not in BAEC. IGFBP-3 stable mRNA levels in BPAE C were increased correspondingly. IGFBP-5 was expressed only in BAEC a nd decreased with exposure to hypoxia. IGFBP-6 mRNA expression was low and increased in both cell types with exposure to hypoxia. These resu lts demonstrate that EC IGFBP baseline expression as well as its expre ssion in hypoxia vary in different vascular beds and suggest that the IGFBPs may be the dominant paracrine regulators of proliferation of EC as well as maintenance oi endothelium integrity during hypoxia.