Mechanosensing role of caveolae and caveolar constituents in human endothelial cells.
A variety of evidence suggests that endothelial cell functions are impaired in altered gravity conditions. Nevertheless, the effects of hypergravity on endothelial cell physiology remain unclear. In this study we cultured primary human endothelial cells under mild hypergravity conditions for 24-48 h, then we evaluated the changes in cell cycle progression, caveolin1 gene expression and in the caveolae status by confocal microscopy. Moreover, we analyzed the activity of enzymes known to be resident in caveolae such as endothelial nitric oxide synthase (eNOS), cycloxygenase 2 (COX-2), and prostacyclin synthase (PGIS). Finally, we performed a three-dimensional in vitro collagen gel test to evaluate the modification of the angiogenic responses. Results indicate that hypergravity shifts endothelial cells to G(0)/G(1) phase of cell cycle, reducing S phase, increasing caveolin1 gene expression and causing an increased distribution of caveolae in the cell interior. Hypergravity also increases COX-2 expression, nitric oxide (NO) and prostacyclin (PGI2) production, and inhibits angiogenesis as evaluated by 3-D collagen gel test, through a pathway not involving apoptosis. Thus, endothelial cell caveolae may be responsible for adaptation of endothelium to hypergravity and the mechanism of adaptation involves an increased caveolin1 gene expression coupled to upregulation of vasodilators as NO and PGI2.
D000222:Adaptation, Physiological / Q000502:physiology; D021941:Caveolae / Q000201:enzymology* / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004727:Endothelium / Q000201:enzymology* / Q000648:ultrastructure; D006801:Humans; D018471:Hypergravity; D007399:Interphase / Q000502:physiology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008465:Mechanoreceptors / Q000201:enzymology* / Q000648:ultrastructure; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D051242:Caveolin 1; D022461:Caveolins; D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase