Endothelial contractile cytoskeleton and microvascular permeability

Qiang Shen, Mack H Wu, Sarah Y Yuan

Division of Research, Department of Surgery, University of California at Davis School of Medicine, Sacramento, CA, USA

Abstract: Microvascular barrier dysfunction represents a significant problem in clinical conditions associated with trauma, burn, sepsis, acute respiratory distress syndrome, ischemia-reperfusion injury, and diabetic retinopathy. An important cellular mechanism underlying microvascular leakage is the generation of contractile force from the endothelial cytoskeleton, which counteracts cell–cell and cell–matrix adhesions leading to paracellular hyperpermeability. In this review, we present recent experimental evidence supporting the critical role of MLCK-activated, RhoA/ROCK-regulated contractile cytoskeleton in endothelial permeability response to inflammatory and thrombotic stimuli arising from thermal injury, activated neutrophils, vascular endothelial growth factor, and fibrinogen degradation products. Further understanding the molecular basis of microvascular barrier structure and function would contribute to the development of novel therapeutic targets for treating circulatory disorders and vascular injury.

Keywords: endothelial cell, contractile cytoskeleton, microvascular permeability, signal transduction