Hypoxia induces differential expression of the integrin receptors alpha(v beta 3) and alpha(v beta 5) cultured human endothelial cells

The integrins alpha(v beta 3) and alpha(v beta 5) have been implicated in p laying a key role in the process of angiogenesis. In this study, we examine d the effects of hypoxia, an important stimulus of angiogenesis, on the dif ferential expression of the integrin subunits beta(3) and beta(5). beta(3) and beta(5) messenger RNA (mRNA), protein levels, and alpha(v)beta(3) funct ion were measured in human umbilical vein endothelial cells (HUVECs) cultur ed under normoxic and hypoxic (1% O-2) conditions. Cells exposed to hypoxic conditions for up to 72 h showed gradually increased mRNA levels of alpha( v) and beta(3), peaking at 24 h, in comparison with cells cultured under no rmoxic conditions. However, beta(5) mRNA levels, under the same hypoxic con ditions, remained at a constant level. Results from Western blot analysis o f HUVECs, cultured under hypoxic conditions, paralleled those of the Northe rn analysis with an increased expression in alpha(v)beta(3) protein levels, measured by blotting with LM609, evident by 24 h. alpha(v)beta(5) protein levels, measured by blotting with P1F6, did not change for up to 72 h. HUVE Cs cultured under hypoxic conditions for 72 h showed increased attachment t o fibrinogen, an alpha(v)beta(3) mediated process. These results indicate t hat hypoxia can increase expression of alpha(v)beta(3) in HUVECs, and that hypoxic regulation of alpha(v)beta(3) may be an important regulator of angi ogenesis. J. Cell. Biochem. 78:674-680, 2000. (C) 2000 Wiley-Liss, Inc.