title: Key role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in pulmonary vascular remodeling and vascular angiogenesis associated with hypoxic pulmonary hypertension.
abstract: We have found that 15-hydroxyeicosatetraenoic acid (15-HETE) induced by hypoxia was an important mediator in the regulation of hypoxic pulmonary hypertension, including the pulmonary vasoconstriction and remodeling. However, the underlying mechanisms of the remodeling induced by 15-HETE are poorly understood. In this study, we performed immunohistochemistry, pulmonary artery endothelial cells migration and tube formation, pulmonary artery smooth muscle cells bromodeoxyuridine incorporation, and cell cycle analysis to determine the role of 15-HETE in hypoxia-induced pulmonary vascular remodeling. We found that hypoxia induced pulmonary vascular medial hypertrophy and intimal endothelial cells migration and angiogenesis, which were mediated by 15-HETE. Moreover, 15-HETE regulated the cell cycle progression and made more smooth muscle cells from the G(0)/G(1) phase to the G(2)/M+S phase and enhanced the microtubule formation in cell nucleus. In addition, we found that the Rho-kinase pathway was involved in 15-HETE-induced endothelial cells tube formation and migration and smooth muscle cell proliferation. Together, these results show that 15-HETE mediates hypoxia-induced pulmonary vascular remodeling and stimulates angiogenesis via the Rho-kinase pathway.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Nangang District, Harbin, Heilongjiang, People's Republic of China.
authors.forename: Cui
authors.initials: C
authors.lastname: Ma
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Shengpan
authors.initials: S
authors.lastname: Niu
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology*; D002417:Cattle; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase; D054460:rho-Associated Kinases