{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:40:16Z","timestamp":1791355216813,"version":"4.3.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2008,9,2]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Despite the therapeutic potential of endothelial progenitor cells (EPCs) in ischemic vascular diseases, their insufficient numbers limit clinical applications. Peroxisome proliferator\u2013activated receptor (PPAR)-\u03b4 belongs to the nuclear hormone receptor superfamily, and its functions in various tissues and cells are almost unexplored, especially with respect to vascular biology.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            PPAR-\u03b4 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-\u03b4 activation with agonist (GW501516 or L-165041) increased the proliferation of human EPCs and protected them from hypoxia-induced apoptosis. In addition, PPAR-\u03b4 activation enhanced EPC functions, such as transendothelial migration, and tube formation. These actions by PPAR-\u03b4 activation in EPCs were dependent on the phosphatidylinositol 3-kinase\/Akt pathway. In ischemic hindlimb of mice models, transplantation of PPAR-\u03b4 agonist\u2013treated human or mouse EPCs enhanced blood flow recovery to ischemic limbs compared with vehicle-treated EPCs. In EPCs from PPAR-\u03b4\u2013knockout mice, however, treatment with PPAR-\u03b4 agonist did not enhance in vivo vasculogenic potential. Systemic administration of PPAR-\u03b4 agonist increased hematopoietic stem cells in bone marrow and EPCs in peripheral blood, leading to improved vasculogenesis with incorporation of bone marrow\u2013derived cells to new vessels in a corneal neovascularization model and limb salvage with better blood flow in an ischemic hindlimb model.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            The results of our study suggest that PPAR-\u03b4 agonist has therapeutic vasculogenic potential for the treatment of ischemic cardiovascular diseases.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.108.777169","type":"journal-article","created":{"date-parts":[[2008,8,19]],"date-time":"2008-08-19T00:50:56Z","timestamp":1219107056000},"page":"1021-1033","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["Peroxisome Proliferator\u2013Activated Receptor-\u03b4 Agonist Enhances Vasculogenesis by Regulating Endothelial Progenitor Cells Through Genomic and Nongenomic Activations of the Phosphatidylinositol 3-Kinase\/Akt Pathway"],"prefix":"10.1161","volume":"118","author":[{"given":"Jung-Kyu","family":"Han","sequence":"first","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Sook","family":"Lee","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Mo","family":"Yang","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hur","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-In","family":"Jun","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gou-Young","family":"Koh","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Peters","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Woo","family":"Park","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., H.-Y.L., H.-J.K., B.-H.O., Y.-B.P., H.-S.K.); Department of Physiology, College of Medicine, Chungnam National University, Daejeon, Korea (C.-H.C.); Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea (G.-Y.K.); Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Jai","family":"Cho","sequence":"additional","affiliation":[{"name":"From the National Research Laboratory for Cardiovascular Stem Cell, College of Medicine, Seoul National University, Seoul, Korea (J.-K.H., H.-S.L., H.-M.Y., J.H., S.-I.J., J.-Y.K., K.-W.P., H.-J.C., 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