COMPARATIVE-STUDIES ON VASCULAR ENDOTHELIUM IN-VITRO .2. HYPOXIA - ITS INFLUENCES ON ENDOTHELIAL-CELL PROLIFERATION AND EXPRESSION OF CELL-ADHESION MOLECULES

Recent studies have presented evidence that the processes of hypoxaemi a and reperfusion are involved in several pathogenetic mechanisms of a therosclerotic lesions. The ability of hypoxaemia to activate circulat ing white blood cells (WBCs) and enhance WBC-endothelial cell (EC) int eractions is suspected to be a major factor in deleterious processes i n the blood vessel wall. Various groups have suggested that cell adhes ion molecules (CAMs), such as ICAM-1, VCAM-1 and E-selectin and their leukocyte ligands are involved in intercellular activities of the rele vant cell types. We studied the effects of different oxygen tensions, simulating normoxic conditions, hypoxia and hyperoxia in vitro with th e help of an umbilical vein EC model in order to determine the effects of oxygenation on CAM presentation on vascular ECs with and without f urther cytokine and endotoxin (lipopolysaccharides; LPS) stimulation. Semiquantitative analysis of ICAM-1, E-selectin and VCAM-1 was perform ed using cell enzyme immunoassay techniques. The presentation of ICAM- 1, Er selectin and VCAM-1 remained on the whole unaffected by both hyp oxia and hyperoxic conditioning after both 7 and 24 h. Stimulation of ICAM-1 by cytokines and LPS was only marginally influenced by the oxyg en tension. Cytokine induction of E-selectin was not affected after 7 h and was even reduced under hypoxia, compared to the control culture after 24 h, while stimulation was increased by hyperoxia. VCAM-1 was r educed in both the hypoxic and hyperoxic culture, while being maximall y stimulated by cytokines and LPS after 7 h. In general, an effect of hypoxia was not found without any further stimulation. Moreover, evide nce is presented that reoxygenation might be the more important aspect in the mechanisms of ischaemia/reperfusion.