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.