Endothelial stress by gravitational unloading: effects on cell growth and cytoskeletal organization.
All organisms on Earth have evolved to survive within the pull of gravity. Orbital space flights have clearly demonstrated that the absence or the reduction of gravity profoundly affects eukaryotic organisms, including man. Because (i). endothelial cells are crucial in the maintenance of the functional integrity of the vascular wall, and (ii). cardiovascular deconditioning has been described in astronauts, we evaluated whether microgravity affected endothelial functions. We show that microgravity reversibly stimulated endothelial cell growth. This effect correlated with an overexpression of heat shock protein 70 (hsp70) and a down-regulation of interleukin 1 alpha (IL-1alpha), a potent inhibitor of endothelial cell growth, also implicated in promoting senescence. In addition, gravitationally unloaded endothelial cells rapidly remodelled their cytoskeleton and, after a few days, markedly down-regulated actin through a transcriptional mechanism. We hypothesize that the reduction in the amounts of actin in response to microgravity represents an adaptative mechanism to avoid the accumulation of redundant actin fibers.
Department of Preclinical Sciences, LITA Vialba, Università di Milano, Via GB Grassi 74, Milan, Italy.
Sofia I M
SI
Carlsson
Maria T S
MT
Bertilaccio
Erica
E
Ballabio
Jeanette A M
JA
Maier
D000199:Actins / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018472:Hypogravity; D007375:Interleukin-1 / Q000378:metabolism
D000199:Actins; D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1