期刊
JOURNAL OF LIPID RESEARCH
卷 52, 期 4, 页码 720-731出版社
ELSEVIER
DOI: 10.1194/jlr.M011007
关键词
cyclooxygenase-pathway; prostaglandin I-synthase; prostacyclin-synthase; prostacyclin; smooth muscle cells; endothelial cells
资金
- Ministerio de Ciencia e Innovacion [SAF2008-01777, SAF2009-09598, SAF2009-11949]
- Red Tematica de Investigacion Cardiovascular (RECAVA) [RD06/0014/0027, RD06/0014/1005]
- Instituto de Salud Carlos III [PS09/01797]
Hypoxia affects vascular function and cell metabolism, survival, growth, and motility; these processes are partially regulated by prostanoids. We analyzed the effect of hypoxia and inflammation on key enzymes involved in prostanoid biosynthesis in human vascular cells. In human vascular smooth muscle cells (VSMC), hypoxia and interleukin (IL)-1 beta synergistically increased prostaglandin (PG)I-2 but not PGE(2) release, thereby increasing the PGI(2)/PGE(2) ratio. Concomitantly, these stimuli upregulated cyclooxygenase-2 (COX-2) expression (mRNA and protein) and COX activity. Interestingly, hypoxia enhanced PGI-synthase (PGIS) expression and activity in VSMC and human endothelial cells. Hypoxia did not significantly modify the inducible microsomal-PGE-synthase (mPGES)-1. Hypoxia-inducible factor (HIF)-1 alpha-silencing abrogated hypoxia-induced PGIS upregulation. PGIS transcriptional activity was enhanced by hypoxia; however, the minimal PGIS promoter responsive to hypoxia (-131 bp) did not contain any putative hypoxia response element (HRE), suggesting that HIF-1 does not directly drive PGIS transcription. Serial deletion and site-directed mutagenesis studies suggested several transcription factors participate cooperatively. Plasma levels of the stable metabolite of PGI(2) and PGIS expression in several tissues were also upregulated in mice exposed to hypoxia.jlr These data suggest that PGIS upregulation is part of the adaptive response of vascular cells to hypoxic stress and could play a role in counteracting the deleterious effect of inflammatory stimuli.-Camacho, M., C. Rodriguez, A. Guadall, S. Alcolea, M. Orriols, J-R. Escudero, J. Martinez-Gonzalez, and L. Vila. Hypoxia upregulates PGI-synthase and increases PGI(2) release in human vascular cells exposed to inflammatory stimuli. J. Lipid Res. 2011. 52: 720-731.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据