Small GTPases in mechanosensitive regulation of endothelial barrier

Alterations in vascular permeability are defining feature of diverse processes including atherosclerosis, inflammation, ischemia/reperfusion injury, and ventilator-induced lung injury. Clinical observations and experimental studies support an essential role of mechanical forces in pathophysiologic regulation of lung barrier. Accumulating data demonstrate that decreased levels of blood flow and increased cyclic stretch of lung tissues associated with lung mechanical ventilation at high tidal volumes increase vascular permeability, activate inflammatory cytokine production, alveolar flooding, leukocyte infiltration, and hypoxemia, and increase morbidity and mortality. Potential synergism between pathologic mechanical stimulation and inflammatory molecules resulting in vascular leak and lung injury becomes increasingly recognized. This review will discuss a role of Rho family of small GTPases in the mechanochemical regulation of pulmonary endothelial permeability associated with ventilator induced lung injury.