[The role of Rho-kinase pathway on PAH].
Anticoagulant agents, vasodilators, and lung transplantation are currently used for the treatment of pulmonary arterial hypertension (PAH); however, more effective treatment needs to be developed. Rho-kinase-mediated pathway plays an important role in various cellular functions, such as vascular smooth muscle hyperconstriction or cell adhesion and motility. We have demonstrated that Rho-kinase is activated in animal models of PAH associated with enhanced pulmonary vasoconstricting and proliferating responses, impaired endothelial vasodilator functions, and pulmonary remodeling and that intravenous fasudil, a selective Rho-kinase inhibitor, exerts acute pulmonary vasodilator effects in patients with severe PAH. Our findings indicate that Rho-kinase is a novel and important therapeutic target of PAH and that Rho-kinase inhibitors are a promising new class of drugs for the disorder.
Fukumoto
Yoshihiro
Y
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
Shimokawa
Hiroaki
H
D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000201:enzymology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D054460:rho-Associated Kinases