title: Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways.
abstract: Human endothelial progenitor cells (hEPCs) derived from bone marrow play a crucial in the prevention of ischemic injuries in the course of postnatal neovasculogenesis. Frequent fish oil (FO) consumption is reportedly associated with a significantly lower incidence of cardiovascular disease. However, the molecular mechanisms of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) are not well elucidated, and the beneficial effect of FO consumption on neovasculogenesis has not been demonstrated yet. In the current study, we investigated the effects of EPA/DHA and FO consumption on neovasculogenesis by using vascular tube formation assay, Western blotting, real-time polymerase chain reaction, immunohistochemical staining and Doppler imaging in both in vitro and in vivo models. The results demonstrate that EPA and DHA dose-dependently enhance the neovasculogenesis and cell migration of hEPCs in vitro. The mechanisms of action included up-regulation of the c-kit protein as well as the phosphorylation of the ERK1/2, Akt and endothelial nitric oxide synthase signaling molecules in hEPCs. Furthermore, EPA significantly suppressed the expression of microRNA 221 in vitro. In experimental animal models, FO consumption significantly induced the formation of new blood vessels (neovasculogenesis) and prevented ischemia. Taken together, it is suggested that FO consumption enhances neovasculogenesis mainly through the effects of EPA in hEPCs, thereby exerting a preventive effect against ischemic injury.
authors.affiliation: Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan, Republic of China; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Shao-Chih
authors.initials: SC
authors.lastname: Chiu
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, Republic of China; NCHU-UCD Plant and Food Biotechnology Program and Agricultural Biotechnology Center (ABC), National Chung Hsing University, Taichung 402, Taiwan, Republic of China.
authors.forename: En-Pei Isabel
authors.initials: EP
authors.lastname: Chiang
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Shu-Yao
authors.initials: SY
authors.lastname: Tsai
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, 40402 Taichung, Taiwan, Republic of China.
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Taipei Medical University, 11031 Taipei, Taiwan, Republic of China.
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Pai
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, 40402 Taichung, Taiwan, Republic of China.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Syu
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, 40402 Taichung, Taiwan, Republic of China.
authors.forename: Ching-Chang
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, USA.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Rodriguez
authors.affiliation: Biomedical Science Laboratory, Department of Nutrition, China Medical University, 40402 Taichung, Taiwan, Republic of China. Electronic address: vincenttang@mail.cmu.edu.tw.
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015118:Eicosapentaenoic Acid; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Eicosapentaenoic acid; Human endothelial progenitor cells; Neovasculogenesis; c-kit; eNOS; microRNA 221