15-脂氧合酶/15-羟廿碳四烯酸在缺氧性肺动脉高压中的作用和机制

Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxic pulmonary arterial hypertension

肺动脉高压是一种病因复杂的罕见病,以肺动脉阻力增高,引起右心室后负荷增大,最终导致右心室功能衰竭而使患者死亡为特征。肺血管花生四烯酸信号通路异常在肺动脉高压中发挥重要作用。肺动脉高压患者肺动脉内皮细胞、平滑肌细胞和成纤维细胞中15-脂氧合酶(15-lipoxygenase,15-LO)及其代谢产物15-羟廿碳四烯酸(15-hydroxyeicosatetraenoic acid,15-HETE)水平均升高。在缺氧条件下,15-LO/15-HETE引起肺动脉收缩,促进肺动脉内皮细胞和平滑肌细胞增殖,抑制肺动脉平滑肌细胞凋亡,促进肺血管外膜纤维化,进而导致肺动脉高压的发生。本文主要对15-LO/15-HETE与缺氧性肺动脉高压相关性的研究进行综述,以阐明15-LO/15-HETE在缺氧性肺动脉高压中发挥的核心作用。

Pulmonary arterial hypertension(PAH)is a rare disease with a complex aetiology characterized by elevated pulmonary artery resistance,which leads to progressive right ventricular failure and ultimately death.The aberrant metabolism of arachidonic acid in the pulmonary vasculature plays a central role in the pathogenesis of PAH.The levels of 15-lipoxygenase(15-LO)and 15-hydroxyeicosatetraenoic acid(15-HETE)are elevated in the pulmonary arterial endothelial cells(PAECs),pulmonary smooth muscle cells(PASMCs)and fibroblasts of PAH patients.Under hypoxia condition,15-LO/15-HETE induces pulmonary artery contraction,promotes the proliferation of PAECs and PASMCs,inhibits apoptosis of PASMCs,promotes fibrosis of pulmonary vessels,and then leads to the occurrence of PAH.Here,we review the research progress on the relationship between 15-LO/15-HETE and hypoxic PAH,in order to clarify the significance of 15-LO/15-HETE in hypoxic PAH.