Rapamycin reduces high-amplitude, mechanical stretch-induced apoptosis in pulmonary microvascular endothelial cells.

Abstract:

: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.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Raaz U,Kuhn H,Wirtz H,Hammerschmidt S

doi

10.1016/j.mvr.2009.01.012

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

297-303

issue

3

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(09)00062-4

journal_volume

77

pub_type

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