The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells

Feng Yen Lin, Nai Wen Tsao, Chun Ming Shih, Yi Wen Lin, Jong Shiua Yeh, Jaw Wen Chen, Hironori Nakagami, Ryuichi Morishita, Tatsuya Sawamura, Chun Yao Huang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Late-outgrowth endothelial progenitor cells (EPCs) are stress-resistant and responsible for reparative functions in the cardiovascular system. Oxidized-LDL (oxLDL) plays a critical role in cardiovascular disease pathogenesis. However, it is largely unknown what the impacts of oxLDL are on late-outgrowth EPCs. This study aimed to investigate the concentration- related effects of oxLDL on EPC functions and related angiogenesis, in vitro and in vivo. In this study, early and late-outgrowth EPCs were generated from circulating human mononuclear cells. oxLDL may regulate EPC vasculogenic function via the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Lower concentrations (5 μg/mL) of oxLDL can potentiate EPC tube formation in vitro and in vivo by activating eNOS mechanisms, which are mediated by p38 MAPK- and SAPK/JNK-related pathways. Higher concentrations of oxLDL (10-50 μg/mL) impaired EPC function via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways and consequent inhibition of eNOS activity, which could be reversed by anti-oxidants (diphenylene iodonium and apocynin) and gp91phox siRNA. In conclusion, oxLDL has concentration-dependent biphasic effects on human late-outgrowth EPC tube formation in vitro and in vivo.

Original languageEnglish
Article number0123971
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - May 1 2015

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Endothelial cells
low density lipoprotein
endothelial cells
stem cells
p38 Mitogen-Activated Protein Kinases
mitogen-activated protein kinase
Class E Scavenger Receptors
Cardiovascular system
cardiovascular system
oxidized low density lipoprotein
Endothelial Progenitor Cells
MAP Kinase Signaling System
small interfering RNA
Cardiovascular System
angiogenesis
NADP
Oxidants
NADP (coenzyme)
oxidants
lectins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells. / Lin, Feng Yen; Tsao, Nai Wen; Shih, Chun Ming; Lin, Yi Wen; Yeh, Jong Shiua; Chen, Jaw Wen; Nakagami, Hironori; Morishita, Ryuichi; Sawamura, Tatsuya; Huang, Chun Yao.

In: PLoS One, Vol. 10, No. 5, 0123971, 01.05.2015.

Research output: Contribution to journalArticle

Lin, Feng Yen ; Tsao, Nai Wen ; Shih, Chun Ming ; Lin, Yi Wen ; Yeh, Jong Shiua ; Chen, Jaw Wen ; Nakagami, Hironori ; Morishita, Ryuichi ; Sawamura, Tatsuya ; Huang, Chun Yao. / The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells. In: PLoS One. 2015 ; Vol. 10, No. 5.
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