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Peroxisome proliferator-activated receptor-delta agonist enhances vasculogenesis by regulating endothelial progenitor cells through genomic and nongenomic activations of the phosphatidylinositol 3-kinase/Akt pathway
DC Field | Value | Language |
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dc.contributor.author | Han, Jung-Kyu | - |
dc.contributor.author | Lee, Hyun-Sook | - |
dc.contributor.author | Yang, Han-Mo | - |
dc.contributor.author | Hur, Jin | - |
dc.contributor.author | Jun, Soo-In | - |
dc.contributor.author | Kim, Ju-Young | - |
dc.contributor.author | Cho, Chung-Hyun | - |
dc.contributor.author | Koh, Gou-Young | - |
dc.contributor.author | Peters, Jeffrey M | - |
dc.contributor.author | Park, Kyung-Woo | - |
dc.contributor.author | Cho, Hyun-Jai | - |
dc.contributor.author | Lee, Hae-Young | - |
dc.contributor.author | Kang, Hyun-Jae | - |
dc.contributor.author | Oh, Byung-Hee | - |
dc.contributor.author | Park, Young-Bae | - |
dc.contributor.author | Kim, Hyo-Soo | - |
dc.date.accessioned | 2010-06-28T05:45:20Z | - |
dc.date.available | 2010-06-28T05:45:20Z | - |
dc.date.issued | 2008-08-20 | - |
dc.identifier.citation | Circulation. 2008;118(10):1021-1033 | en |
dc.identifier.issn | 1524-4539 (Electronic) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18711014 | - |
dc.identifier.uri | http://circ.ahajournals.org/cgi/reprint/118/10/1021.pdf | - |
dc.identifier.uri | https://hdl.handle.net/10371/67930 | - |
dc.description.abstract | BACKGROUND: Despite the therapeutic potential of endothelial progenitor cells (EPCs) in ischemic vascular diseases, their insufficient numbers limit clinical applications. Peroxisome proliferator-activated receptor (PPAR)-delta belongs to the nuclear hormone receptor superfamily, and its functions in various tissues and cells are almost unexplored, especially with respect to vascular biology. METHODS AND RESULTS: PPAR-delta activation in EPCs phosphorylated Akt, and this phosphorylation was mediated not only by genomic but also by nongenomic pathways through interaction with the regulatory subunit of phosphatidylinositol 3-kinase. PPAR-delta activation with agonist (GW501516 or L-165041) increased the proliferation of human EPCs and protected them from hypoxia-induced apoptosis. In addition, PPAR-delta activation enhanced EPC functions, such as transendothelial migration, and tube formation. These actions by PPAR-delta activation in EPCs were dependent on the phosphatidylinositol 3-kinase/Akt pathway. In ischemic hindlimb of mice models, transplantation of PPAR-delta agonist-treated human or mouse EPCs enhanced blood flow recovery to ischemic limbs compared with vehicle-treated EPCs. In EPCs from PPAR-delta-knockout mice, however, treatment with PPAR-delta agonist did not enhance in vivo vasculogenic potential. Systemic administration of PPAR-delta agonist increased hematopoietic stem cells in bone marrow and EPCs in peripheral blood, leading to improved vasculogenesis with incorporation of bone marrow-derived cells to new vessels in a corneal neovascularization model and limb salvage with better blood flow in an ischemic hindlimb model. CONCLUSIONS: The results of our study suggest that PPAR-delta agonist has therapeutic vasculogenic potential for the treatment of ischemic cardiovascular diseases. | en |
dc.language.iso | en | en |
dc.publisher | American Heart Association | en |
dc.subject | 1-Phosphatidylinositol 3-Kinase/*metabolism | en |
dc.subject | Animals | en |
dc.subject | Blood Flow Velocity/drug effects | en |
dc.subject | Bone Marrow/metabolism | en |
dc.subject | Cells, Cultured | en |
dc.subject | Corneal Neovascularization/metabolism/pathology | en |
dc.subject | Disease Models, Animal | en |
dc.subject | Endothelial Cells/*metabolism/pathology | en |
dc.subject | Female | en |
dc.subject | Hematopoietic Stem Cells/*metabolism/pathology | en |
dc.subject | Hindlimb/metabolism/pathology | en |
dc.subject | Humans | en |
dc.subject | Ischemia/*metabolism/pathology/therapy | en |
dc.subject | Male | en |
dc.subject | Mice | en |
dc.subject | Mice, Knockout | en |
dc.subject | Neovascularization, Physiologic/*drug effects | en |
dc.subject | PPAR delta/*agonists/metabolism | en |
dc.subject | Proto-Oncogene Proteins c-akt | en |
dc.subject | Stem Cell Transplantation | en |
dc.subject | Thiazoles/*pharmacology | en |
dc.subject | Vascular Diseases/*metabolism/pathology/therapy | en |
dc.title | Peroxisome proliferator-activated receptor-delta agonist enhances vasculogenesis by regulating endothelial progenitor cells through genomic and nongenomic activations of the phosphatidylinositol 3-kinase/Akt pathway | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 한정규 | - |
dc.contributor.AlternativeAuthor | 이현숙 | - |
dc.contributor.AlternativeAuthor | 양한모 | - |
dc.contributor.AlternativeAuthor | 허진 | - |
dc.contributor.AlternativeAuthor | 전수인 | - |
dc.contributor.AlternativeAuthor | 김주영 | - |
dc.contributor.AlternativeAuthor | 조정현 | - |
dc.contributor.AlternativeAuthor | 조현재 | - |
dc.contributor.AlternativeAuthor | 이해영 | - |
dc.contributor.AlternativeAuthor | 강현재 | - |
dc.contributor.AlternativeAuthor | 오병희 | - |
dc.contributor.AlternativeAuthor | 박영배 | - |
dc.contributor.AlternativeAuthor | 김효수 | - |
dc.contributor.AlternativeAuthor | 고규영 | - |
dc.identifier.doi | 10.1161/CIRCULATIONAHA.108.777169 | - |
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