Effects of retinoids on endothelial cell proliferation, prostacyclin production and platelet aggregation

In addition to their anti-inflammatory and anti-cancer activities, retinoids have been shown to affect angiogenesis, endothelial proliferation and the process of wound healing. While peripheral vascular occlusion has not been observed as an adverse effect clinically, the effects of retinoids on prostacyclin production in endothelial cells and platelet aggregation are not known. We examined the effects of tretinoin, isotretinoin and etretinate (3.3 x 10(-8) to 3.3 x 10(-5) M) on cytotoxicity by 51Cr-release assay, growth and prostacyclin in bovine carotid endothelial cell cultures, and the aggregation of human platelets induced by ADP. All retinoids showed either no or only small effects on cytotoxicity and human platelet aggregation. Prostacyclin production was not significantly affected except for tretinoin and isotretinoin at 3.3 x 10(-5) M. Endothelial proliferation was affected by all three retinoids in a dose-dependent fashion; for tretinoin and isotretinoin an inhibitory trend was noted as the concentration increased but the reverse was true for etretinate. Retinoids at 3.3 x 10(-5) M induced alterations of typical endothelial morphology; the cells became fibroblastoid. The results of prostacyclin production and platelet aggregation in the present study are consistent with the absence of peripheral vascular occlusion as a side effect clinically.