title: Rho-kinase as a potential therapeutic target for the treatment of pulmonary hypertension.
abstract: Pulmonary hypertension (PH) is a cardiovascular disorder characterized by vasoconstriction and vascular remodeling. Recently, rapidly increasing evidence from various rat models of PH and patients with PH suggest that small GTPase Rho and its downstream effector, Rho-kinase, play a key role in the pathogenesis of PH. Activation of the Rho/Rho-kinase pathway is important for pulmonary endothelial dysfunction, pulmonary vascular smooth muscle cell contractility, proliferation and apoptosis in PH. A greater Rho-kinase expression and an enhanced Rho-kinase activity have been observed in pulmonary arteries of PH rats, such as hypoxia-induced, monocrotaline-induced and genetic spontaneous PH rats. Moreover, Y-27632 or fasudil, the selective Rho-kinase inhibitors, significantly attenuated PH in various pulmonary hypertensive model rats and patients with PH, but did not reduce systemic blood pressure. Therefore, Rho-kinase inhibitors may have therapeutic potential for the treatment of PH.
authors.affiliation: Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xi-Qian
authors.initials: XQ
authors.lastname: Xing
authors.forename: Ye
authors.initials: Y
authors.lastname: Gan
authors.forename: Shang-Jie
authors.initials: SJ
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Xiang
mesh_terms: D000818:Animals; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein