Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways

Shao Chih Chiu, En Pei Isabel Chiang, Shu Yao Tsai, Fu Yu Wang, Man Hui Pai, Jia Ning Syu, Ching Chang Cheng, Raymond L. Rodriguez, Feng Yao Tang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)934-945
Number of pages12
JournalJournal of Nutritional Biochemistry
Volume25
Issue number9
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Proto-Oncogene Proteins c-kit
Eicosapentaenoic Acid
Fish Oils
Endothelial cells
Docosahexaenoic Acids
Blood Vessels
Phosphorylation
Nitric Oxide Synthase Type III
Polymerase chain reaction
Wounds and Injuries
Blood vessels
MicroRNAs
Cell Movement
Real-Time Polymerase Chain Reaction
Assays
Bone
Animals
Cardiovascular Diseases
Up-Regulation
Ischemia

Keywords

  • Akt
  • C-kit
  • Eicosapentaenoic acid
  • ENOS
  • Human endothelial progenitor cells
  • MicroRNA 221
  • Neovasculogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Medicine(all)

Cite this

Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways. / Chiu, Shao Chih; Chiang, En Pei Isabel; Tsai, Shu Yao; Wang, Fu Yu; Pai, Man Hui; Syu, Jia Ning; Cheng, Ching Chang; Rodriguez, Raymond L.; Tang, Feng Yao.

In: Journal of Nutritional Biochemistry, Vol. 25, No. 9, 2014, p. 934-945.

Research output: Contribution to journalArticle

Chiu, Shao Chih ; Chiang, En Pei Isabel ; Tsai, Shu Yao ; Wang, Fu Yu ; Pai, Man Hui ; Syu, Jia Ning ; Cheng, Ching Chang ; Rodriguez, Raymond L. ; Tang, Feng Yao. / Eicosapentaenoic acid induces neovasculogenesis in human endothelial progenitor cells by modulating c-kit protein and PI3-K/Akt/eNOS signaling pathways. In: Journal of Nutritional Biochemistry. 2014 ; Vol. 25, No. 9. pp. 934-945.
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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

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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.

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