Key Role of ROS in the Process of 15-Lipoxygenase-15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary HypertensionReportar como inadecuado




Key Role of ROS in the Process of 15-Lipoxygenase-15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

We previously reported that 15-lipoxygenase 15-LO and its metabolite 15-hydroxyeicosatetraenoic acid 15-HETE were up-regulated in pulmonary arterial cells from both pulmonary artery hypertension patients and hypoxic rats and that these factors mediated the progression of pulmonary hypertension PH by affecting the proliferation and apoptosis of pulmonary arterial PA cells. However, the underlying mechanisms of the remodeling induced by 15-HETE have remained unclear. As reactive oxygen species ROS and 15-LO are both induced by hypoxia, it is possible that ROS are involved in the events of hypoxia-induced 15-LO expression that lead to PH. We employed immunohistochemistry, tube formation assays, bromodeoxyuridine BrdU incorporation assays, and cell cycle analyses to explore the role of ROS in the process of 15-HETE-mediated hypoxic pulmonary hypertension HPH. We found that exogenous 15-HETE facilitated the generation of ROS and that this effect was mainly localized to mitochondria. In particular, the mitochondrial electron transport chain and nicotinamide-adenine dinucleotide phosphate oxidase 4 Nox4 were responsible for the significant 15-HETE-stimulated increase in ROS production. Moreover, ROS induced by 15-HETE stimulated endothelial cell EC migration and promoted pulmonary artery smooth muscle cell PASMC proliferation under hypoxia via the p38 MAPK pathway. These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling PVR via the p38 MAPK pathway.



Autor: Qian Li , Min Mao , Yanli Qiu, Gaofeng Liu, Tingting Sheng, Xiufeng Yu, Shuang Wang, Daling Zhu

Fuente: http://plos.srce.hr/



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