Journal
MICROVASCULAR RESEARCH
Volume 77, Issue 3, Pages 297-303Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2009.01.012
Keywords
Mechanical stretch; Cell death; Cytoskeleton
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Alveolar epithelial and endothelial cell death caused by mechanical over-distension is likely to contribute to ventilator-induced lung injury (VILI). Consequently, the search for cytoprotective interventions is of interest. We investigated the effect of the mTOR inhibitor rapamycin on human pulmonary microvascular endothelial cell (HMVEC-L) viability in a model of high-amplitude mechanical stretch. Cyclic mechanical stretch (30% increase in membrane surface area, cycling frequency 40/min), employed for 24 h induced apoptosis in HMVEC-L This effect was reduced by rapamycin treatment. Focusing on possible mechanisms of action we demonstrated that the stretch-induced reduction in the anti-apoptotic messenger pAkt could be restored by rapamycin treatment Furthermore, we observed rapamycin-induced modifications in the HMVEC-L actin cytoskeleton architecture and global cellular f-actin content which functionally resulted in an increased global cellular mechanical stability - as indicated by an increased HMVEC-L osmomechanical resistance thereby possibly desensitizing HMVEC-L to mechanical stimulation. According to the data from the present study, rapamycin represents a promising cytoprotective agent under mechanically challenging conditions such as mechanical ventilation. (C) 2009 Elsevier Inc. All rights reserved.
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