Abstract:
:The role of prostaglandin production in the control of regenerative function of endothelial progenitor cells (EPCs) has not been studied. We hypothesized that activation of cyclooxygenase (COX) enzymatic activity and the subsequent production of prostacyclin (PGI(2)) is an important mechanism responsible for the regenerative function of EPCs. In the present study, we detected high levels of COX-1 protein expression and PGI(2) biosynthesis in human EPCs outgrown from blood mononuclear cells. Expression of COX-2 protein was almost undetectable under basal conditions but significantly elevated after treatment with tumor necrosis factor-alpha. Condition medium derived from EPCs hyperpolarized human coronary artery smooth muscle cells, similar to the effect of the PGI(2) analog iloprost. The proliferation and in vitro tube formation by EPCs were inhibited by the COX inhibitor indomethacin or by genetic inactivation of COX-1 or PGI(2) synthase with small interfering (si)RNA. Impaired tube formation and cell proliferation induced by inactivation of COX-1 were rescued by the treatment with iloprost or the selective peroxisome proliferator-activated receptor (PPAR)delta agonist GW501516 but not by the selective PGI(2) receptor agonist cicaprost. Downregulation of PPARdelta by siRNA also reduced angiogenic capacity of EPCs. Iloprost failed to reverse PPARdelta siRNA-induced impairment of angiogenesis. Furthermore, transfection of PGI(2) synthase siRNA, COX-1 siRNA, or PPARdelta siRNA into EPCs decreased the capillary formation in vivo after transplantation of human EPCs into the nude mice. These results suggest that activation of COX-1/PGI(2)/PPARdelta pathway is an important mechanism underlying proangiogenic function of EPCs.
journal_name
Circ Resjournal_title
Circulation researchauthors
He T,Lu T,d'Uscio LV,Lam CF,Lee HC,Katusic ZSdoi
10.1161/CIRCRESAHA.108.176057subject
Has Abstractpub_date
2008-07-03 00:00:00pages
80-8issue
1eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.108.176057journal_volume
103pub_type
杂志文章abstract::Dystrophin has a key role in striated muscle mechanotransduction. In mice lacking the gene encoding for dystrophin (mdx mice), the absence of dystrophin and several other proteins of the dystrophin-glycoprotein complex induces a defect in flow (shear stress)-mediated NO-dependent dilation (FMD). Because the endotheliu...
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abstract:RATIONALE:Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE:We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow...
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pub_type: 杂志文章,评审
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更新日期:2008-08-01 00:00:00
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更新日期:2001-03-16 00:00:00
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更新日期:2004-04-16 00:00:00
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更新日期:2001-01-19 00:00:00
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更新日期:1992-04-01 00:00:00
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更新日期:2001-05-25 00:00:00
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更新日期:2013-02-01 00:00:00
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doi:10.1161/CIRCRESAHA.111.246124
更新日期:2011-09-16 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.53.6.731
更新日期:1983-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.45.4.479
更新日期:1979-10-01 00:00:00
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更新日期:1988-08-01 00:00:00
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更新日期:2011-09-30 00:00:00
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更新日期:1982-08-01 00:00:00
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更新日期:1994-04-01 00:00:00
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更新日期:1991-04-01 00:00:00
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更新日期:1989-12-01 00:00:00
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更新日期:1987-05-01 00:00:00
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更新日期:2000-11-24 00:00:00
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pub_type: 杂志文章
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更新日期:1994-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:1978-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1990-10-01 00:00:00