Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals.
Health hazards in astronauts are represented by cardiovascular problems and impaired bone healing. These disturbances are characterized by a common event, the loss of function by vascular endothelium, leading to impaired angiogenesis. We investigated whether the exposure of cultured endothelial cells to hypogravity condition could affect their behaviour in terms of functional activity, biochemical responses, morphology, and gene expression. Simulated hypogravity conditions for 72 h produced a reduction of cell number. Genomic analysis of endothelial cells exposed to hypogravity revealed that proapoptotic signals increased, while antiapoptotic and proliferation/survival genes were down-regulated by modelled low gravity. Activation of apoptosis was accompanied by morphological changes with mitochondrial disassembly and organelles/cytoplasmic NAD(P)H redistribution, as evidenced by autofluorescence analysis. In this condition cells were not able to respond to angiogenic stimuli in terms of migration and proliferation. Our study documents functional, morphological, and transcription alterations in vascular endothelium exposed to simulated low gravity conditions, thus providing insights on the occurrence of vascular tissue dysregulation in crewmen during prolonged space flights. Moreover, the alteration of vascular endothelium can intervene as a concause in other systemic effects, like bone remodelling, observed in weightlessness.
Morbidelli
Lucia
L
Section of Pharmacology, Department of Molecular Biology and C.R.I.S.M.A., University of Siena, Siena, Italy. morbidelli@unisi.it
Monici
Monica
M
Marziliano
Nicola
N
Cogoli
Augusto
A
Fusi
Franco
F
Waltenberger
Johannes
J
Ziche
Marina
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D018474:Weightlessness Simulation / Q000379:methods*
D016207:Cytokines