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The differential response to microgravity of micro- and macro-vascular endothelial cells.   J.A.M. Maier, S. Cotrupi, University of Milan, Dept. Preclinical Sciences - LITA Vialba, Via G.B. Grassi 74, Milan 20157, Italy.

   Microgravity is known to have adverse effects on the eukaryotic cell. Here we report that microgravity affects the behaviour of vascular endothelial cells, which are crucial to maintain the functional integrity of the vascular wall. To simulate microgravity we have utilized a NASA-developed bioreactor, the Rotating Wall Vessels (RWV). Within 24 hours, human umbilical vein endothelial cells (HUVE) were overexpressing the heat shock protein 70 (hsp70) and downregulating interleukin (IL)-1 alpha, a potent inhibitor of endothelial cell growth, also implicated in promoting senescence. Within just 4 hours, the RWV-cultured cells displayed marked morphological alterations and, after a few days, down-regulated the structural protein actin. The adaptative responses to simulated microgravity are reversible.

   Surprisingly, microvascular endothelial cells cultured in the RWV did not upregulate hsp70 and were growth inhibited. This latter event is due to the overexpression of p21, an inhibitor of the cyclin-CDK2 complexes that are necessary for the transition from the G1 to the S phase of the cell cycle. In the RWV, microvascular cells did not modulate the levels of IL-1, but they downregulated IL-6 as detected by protein array and confirmed by western blot.

   We conclude that micro- and macro-vascular endothelial cells activate different pathway in response to simulated microgravity.

(Supported by ESA)