Endothelial cell responses to hypoxia: initiation of a cascade of cellularinteractions

The origin of several vascular pathologies involves sudden or recurrent oxy gen deficiency. In this review, we examine what the biochemical and molecul ar responses of the endothelial cells to the lack of oxygen are and how the se responses may account for the features observed in pathological situatio ns, mainly by modifications of cell-cell interactions. Two major responses of the endothelial cells have been observed depending on the degree and dur ation of the oxygen deficiency. Firstly, acute hypoxia rapidly activates th e endothelial cells to release inflammatory mediators and growth factors. T hese inflammatory mediators are able to recruit and promote the adherence o f neutrophils to the endothelium where they become activated. The synthesis of platelet-activating factor plays a key role in this adherence process. Secondly, longer periods of hypoxia increase the expression of specific gen es such as those encoding some cytokines as well as for the growth factors platelet-derived growth factor and vascular endothelial growth factor. The transcriptional induction of these genes is mediated through the activation of several transcription factors, the most important one being hypoxia ind ucible factor-1. The link between our knowledge of the signalling cascade o f the cellular and molecular events initiated by hypoxia and their involvem ent in several vascular pathological situations, Varicose veins, tumor angi ogenesis and pulmonary hypertension is discussed briefly. (C) 2000 Elsevier Science B.V. All rights reserved.