Hypoxia promotes rabbit pulmonary artery smooth muscle cells proliferation through a 15-LOX-2 product 15(S)-hydroxyeicosatetraenoic acid

详细信息    查看全文

• 作者：Ruihui Shan^a ; Li Chen^a ; Xinyu Li^a ; Hong Wu^b ; Qingcheng Liang^c ; ^{Qingcheng_Liang@yahoo.com.cn} ; Xiaobo Tang^a ; ^{ty6163@yahoo.com.cn}
• 关键词：15(S)-hydroxyeicosatetraenoic acid ; Proliferation ; Hypoxia ; Mitogen-activated protein kinases ; Extracellular signal-regulated kinase-1/extracellular signal-regulated kinase-2
• 刊名：Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA)
• 出版年：2012
• 出版时间：January-February 2012
• 年：2012
• 卷：86
• 期：1-2
• 页码：85-90
• 全文大小：688 K

文摘

The initial event of hypoxic pulmonary hypertension is acute hypoxic pulmonary vasoconstriction followed by remodeling of pulmonary arteries. Although 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] is found to be able to induce hypoxic pulmonary vasoconstriction, role of 15(S)-HETE in pulmonary artery smooth muscle cells (PASMCs) proliferation has been studied less. We sought evidence for a role of 15(S)-HETE in the development of hypoxia-induced pulmonary hypertension. We found that hypoxia enhances 15-lipoxygenase-2 (15-LOX-2) expression and stimulates cultured rabbit PASMCs proliferation. 15(S)-HETE at concentration 0.1 ¦ÌM stimulated proliferation of PASMCs and induced ERK 1/ERK 2 phosphorylation but had no effect on p38 kinase expression as assessed by Western blotting. 15(S)-HETE-stimulated PASMC proliferation was blocked by the MEK inhibitors PD-98059. Hypoxia (3 % O₂)-stimulated PASMC proliferation was blocked by U0126, a MEK inhibitor, as well as by NDGA and CDC, inhibitors of 15-LOX, but not by the p38 MAPK inhibitor SB-202190. We conclude that 15-LOX-2 and its product, 15(S)-HETE, are important intermediates in hypoxia-induced rabbit PASMC proliferation and may participate in hypoxia-induced pulmonary hypertension.