ENDOTHELIAL-CELL HYPOXIA ASSOCIATED PROTEINS ARE CELL AND STRESS SPECIFIC

Vascular endothelial cells (EC) are one of the initial cells exposed t o decreases in blood oxygen tension. Bovine EC respond not only by alt ering secretion of vasoactive, mitogenic, and thrombogenic substances, but also by developing adaptive mechanisms in order to survive acute and chronic hypoxic exposures. EC exposed to hypoxia in vitro upregula te a unique set of stress proteins of Mr 34, 36, 39, 47, and 56 kD. Pr evious studies have shown that these proteins are cell associated, upr egulated in a time and oxygen-concentration dependent manner, and are distinct from heat shock (HSPs) and glucose-regulated proteins (GRPs). To further characterize these hypoxia-associated proteins (HAPs), we investigated their upregulation in human EC from various vascular beds and compared this to possible HAP upregulation in other cell types. H uman aortic, pulmonary artery, and microvascular EC upregulated the sa me set of proteins in response to hypoxia. In comparison, neither lung fibroblasts, pulmonary artery smooth muscle cells, pulmonary alveolar type II cells, nor renal tubular epithelial cells upregulated protein s of these Mr. Instead, most of these cell types induced synthesis of proteins of Mrs corresponding to either HSPs, GRPs, or both. Further s tudies demonstrated that exposure of EC to related stresses such as cy anide, 2-deoxyglucose, hydrogen peroxide, dithiothreitol, and glucose deprivation did not cause upregulation of HAPs. Evaluation of cellular damage during hypoxia using phase-contrast microscopy, trypan blue ex clusion, chromium release, and adherent cell counts showed that EC sur vived longer with less damage than any of the above cell types. The in duction of HAPs, and the lack of induction of HSPs or GRPs, by EC in r esponse to hypoxia may be related to their unique ability to tolerate hypoxia for prolonged periods. (C) 1993 Wiley-Liss, Inc.