Caveolae and caveolae constituents in mechanosensing: effect of modelled microgravity on cultured human endothelial cells.

Studies in modelled microgravity or during orbital space flights have clearly demonstrated that endothelial cell physiology is strongly affected by the reduction of gravity. Nevertheless, the molecular mechanisms by which endothelial cells may sense gravity force remain unclear. We previously hypothesised that endothelial cell caveolae could be a mechanosensing system involved in hypergravity adaptation of human endothelial cells. In this study, we analysed the effect on the physiology of human umbilical vein endothelial cell monolayers of short exposure to modelled microgravity (24-48 h), obtained by clinorotation. For this purpose, we evaluated the levels of compounds, such as nitric oxide (NO) and prostacyclin (PGI2), involved in vascular tone regulation and synthesized starting from caveolae-related enzymes. Furthermore, we examined post translational modifications of Caveolin-1 (Cav-1), induced by simulated microgravity. The results we collected clearly indicated that short microgravity exposure strongly affected endothelial nitric oxide synthase (eNOS) activity associated with Cav-1 (Tyr 14) phosphorylation, without modifying the angiogenic response of human umbilical vein endothelial (HUVE) cells. We propose here that one of the early molecular mechanisms responsible for gravity sensing of endothelium involves endothelial cell caveolae and Cav-1 phosphorylation.