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: Cui Ma, Yaqian Li, Jun Ma, Yun Liu, Qian Li, Shengpan Niu, Zhiying Shen, Lei Zhang, Zhenwei Pan, Daling Zhu
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 58 Issue 4 Pg. 679-88 (Oct 2011) ISSN: 1524-4563 [Electronic] United States
• PMID: 21859965 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxyeicosatetraenoic Acids
• 15-hydroxy-5,8,11,13-eicosatetraenoic acid
• Arachidonate 15-Lipoxygenase
• rho-Associated Kinases

Topics

• Animals
• Arachidonate 15-Lipoxygenase (physiology)
• Cattle
• Cell Cycle (physiology)
• Cell Movement (physiology)
• Cell Proliferation
• Cells, Cultured
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Endothelium, Vascular (pathology, physiopathology)
• Humans
• Hydroxyeicosatetraenoic Acids (physiology)
• Hypertension, Pulmonary (pathology, physiopathology)
• Hypoxia (physiopathology)
• Male
• Models, Animal
• Muscle, Smooth, Vascular (pathology, physiopathology)
• Neovascularization, Pathologic (pathology, physiopathology)
• Pulmonary Artery (pathology, physiopathology)
• Rats
• Rats, Wistar
• Signal Transduction (physiology)
• rho-Associated Kinases (physiology)