Endothelial cells in culture: a model to study in vitro vascular toxicity.
This review discusses the importance of cultured endothelial cells in the evaluation of the potential toxicity of a drug and for understanding the toxic effects of some compounds on the vascular system. Vascular toxicity is observed when subjects are exposed to chemicals present in the air or after ingestion of xenobiotics or drugs. Furthermore, some drugs can lead to side-effects owing to an alteration of endothelial cell function. Endothelial cells of human and animal origin can be cultured and several of their properties can be studied using different experimental systems. Cyclosporin and penicillamine have been shown to reduce angiogenesis in vitro, as has also been reported for monocrotaline pyrrole. Other components, such as pyrrolizidine alkaloid, were found to be cytotoxic, as demonstrated by chromium-51 or lactate dehydrogenase release. More subtle changes can be detected in peroxidation, phospholipase activity and prostacyclin production. Endothelial cells cultured to confluency can be used to measure in vitro permeability to radiolabelled inulin or albumin. Tunicamycin, an inhibitor of glycosylation, increases permeability. Xenobiotics such as lead inhibit the production of plasminogen activator (t-PA) or by disrupting the thromboxane-A(2)/prostacyclin balance, which promotes a thrombotic process.
Chappey
O
O
Laboratoire de Biologie Vasculaire et Cellulaire, EA 1557, U294 INSERM, CHU Lariboisière, U. Paris 7, Paris, France.
Wautier
M P
MP
Wautier
J L
JL