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Title: Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

Abstract

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.

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [1]
  1. Section of Pharmacology, Department of Molecular Biology and C.R.I.S.M.A., University of Siena, Siena (Italy)
  2. CEO-Centro di Eccellenza Optronica, Firenze (Italy)
  3. Laboratorio di Genetica Molecolare, IRCCS Policlinico San Matteo, Pavia (Italy)
  4. Space Biology, ETH Zurich (Switzerland)
  5. Department of Clinical Physiopathology, University of Florence, Florence (Italy)
  6. Department of Interventional Cardiology, University of Maastricht (Netherlands)
Publication Date:
OSTI Identifier:
20710928
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 334; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.06.124; PII: S0006-291X(05)01369-0; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CONSTITUENTS; CELL PROLIFERATION; ENDOTHELIUM; GENES; HEALING; HEALTH HAZARDS; MORPHOLOGICAL CHANGES; MORPHOLOGY; NAD; SKELETON; STIMULI; TRANSCRIPTION; WEIGHTLESSNESS

Citation Formats

Morbidelli, Lucia, Monici, Monica, Marziliano, Nicola, Cogoli, Augusto, Fusi, Franco, Waltenberger, Johannes, and Ziche, Marina. Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.06.124.
Morbidelli, Lucia, Monici, Monica, Marziliano, Nicola, Cogoli, Augusto, Fusi, Franco, Waltenberger, Johannes, & Ziche, Marina. Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals. United States. https://doi.org/10.1016/j.bbrc.2005.06.124
Morbidelli, Lucia, Monici, Monica, Marziliano, Nicola, Cogoli, Augusto, Fusi, Franco, Waltenberger, Johannes, and Ziche, Marina. 2005. "Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals". United States. https://doi.org/10.1016/j.bbrc.2005.06.124.
@article{osti_20710928,
title = {Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals},
author = {Morbidelli, Lucia and Monici, Monica and Marziliano, Nicola and Cogoli, Augusto and Fusi, Franco and Waltenberger, Johannes and Ziche, Marina},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2005.06.124},
url = {https://www.osti.gov/biblio/20710928}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 334,
place = {United States},
year = {Fri Aug 26 00:00:00 EDT 2005},
month = {Fri Aug 26 00:00:00 EDT 2005}
}