TY - JOUR
T1 - Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways
AU - Chiu, Shao Chih
AU - Chiang, En Pei Isabel
AU - Tsai, Shu Yao
AU - Wang, Fu Yu
AU - Pai, Man Hui
AU - Syu, Jia Ning
AU - Cheng, Ching Chang
AU - Rodriguez, Raymond L.
AU - Tang, Feng Yao
N1 - Funding Information:
Financial support: This material is based upon work supported, in part, by the Ministry of Education, Taiwan, R.O.C. , under the ATU plan, National Science Council grant, under Agreements NSC-100-2320-B-039-003, 100-2628-B005-002-MY4, 100-2314-B-039-005, 101-2314-B-039-011, 101-2320-B-039-054-MY3, 101-2320-B-005-006-MY3, 101-2811-B-039-024 and 102-2811-B-039-035 and China Medical University (CMU) grant under Agreements CMU101-Award-10 CMU, 100-ASIA-11, CMU101-ASIA-3, CMU101-S-25, CMU 102-S-05 and DMR-103-057 . Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the Ministry of Education, National Science Council, National Chung Hsing University, Asia University, Taipei Medical University, University of California Davis and China Medical University.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Akt
KW - C-kit
KW - ENOS
KW - Eicosapentaenoic acid
KW - Human endothelial progenitor cells
KW - MicroRNA 221
KW - Neovasculogenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=84905217171&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2014.04.007
DO - 10.1016/j.jnutbio.2014.04.007
M3 - Article
C2 - 24927915
AN - SCOPUS:84905217171
VL - 25
SP - 934
EP - 945
JO - Nutrition Reports International
JF - Nutrition Reports International
SN - 0955-2863
IS - 9
ER -
