Mechanical Forces Stimulate Endothelial Microparticle Generation via Caspase-Dependent Apoptosis-Independent Mechanism

Abstract

Microparticle release by vascular endothelium has been implicated in various cardiovascular pathologies. Ventilator-induced lung injury (VILI) is a life-threatening complication of mechanical ventilation at high tidal volumes associated with excessive mechanical stretch of pulmonary vascular endothelial cells. However, a role of VILI-relevant levels of cyclic stretch in microparticle generation by vascular endothelium remains unknown. We report microparticle formation by human pulmonary endothelial cells exposed to pathologic, but not physiologic, levels of mechanical stress. Stretch-induced microparticle generation was not affected by cell co-treatment with inflammatory agents thrombin or bacterial wall lipopolysacharide. Neither the basal nor the pathologic cyclic stretch-induced microparticle production was affected by Rho kinase and calpain inhibitors, but were instead abolished by caspase inhibitor. In contrast to lipopolysacharide, pathologic mechanical strain did not significantly induce apoptosis in pulmonary endothelial cells. These results show for the first time that mechanical strain of pulmonary endothelial cells at levels relevant to high tidal volume mechanical ventilation is a potent activator of microparticle formation, which requires caspase activity; however, this mechanism is independent of apoptosis. These results suggest a novel mechanism that may contribute to VILI-associated vascular dysfunction.

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Topics

Apoptosis
Endothelin and Endothelium & Epithelium and Epithelial Transport

Authors

Anne Clémence Vion, Anna A. Birukova, Chantal M. Boulanger, Konstantin G. Birukov

Published in:

Pulmonary Circulation Vol 3: No 1 cover image

March 2013

Pulmonary Circulation Vol 3: No 1

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