The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension

Bobby   D.   Nossaman; Philip   J.   Kadowitz

doi:10.2174/157016309787581057

Abstract

The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation, and restenosis; and that the inhibition of rho-kinase has been shown to have a beneficial effect in a variety of cardiovascular disorders. It is our hypothesis that rho-kinase inhibitors promote vasodilation independent of the mechanism that increases vasoconstrictor tone and moreover, the RhoA/rho-kinase pathway has a role in the regulation of smooth muscle tone under physiological conditions. The objective of this review is to improve our current understanding of the role of RhoA/rho-kinase pathway in the regulation of vasoconstrictor tone and the use of rho-kinase inhibitors in the treatment of cardiovascular disorders with an emphasis on pulmonary hypertension.

Keywords: Intracellular signaling peptides and proteins, protein kinases, RhoA/rho-kinase pathway, muscle, smooth, vascular, pulmonary hypertension, pulmonary vascular bed, systemic vascular bed, signal transduction, inhibitors/pharmacology, cardiovascular diseases, fasudil, HA-1077, Y-27632