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Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway.

Publication ,  Journal Article
Tie, G; Yan, J; Yang, Y; Park, BD; Messina, JA; Raffai, RL; Nowicki, PT; Messina, LM
Published in: J Vasc Res
2010

We tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induced EPC apoptosis. Hypercholesterolemic ApoE null mice had a significant reduction of the phosphorylated Akt (p-Akt)/Akt ratio in EPCs, as well as a greater percentage of apoptosis in these cells than EPCs isolated from wild-type (WT) C57Bl/6 mice. EPCs were isolated from WT spleen and exposed to oxLDL in vitro. oxLDL increased O₂⁻ and H₂O₂ in these cells and induced a dose- and time-dependent reduction in the p-Akt/Akt ratio and increase in EPC apoptosis. These effects were significantly reduced by the antioxidants superoxide dismutase, L-NAME, epicatechin and FeTPPs. oxLDL also induced nitrosylation of the p85 subunit of PI3K and subsequent dissociation of the p85 and p110 subunits, an effect significantly reduced by all the antioxidant agents tested. EPC transfection with a constitutively active Akt isoform (Ad-myrAkt) significantly reduced oxLDL-induced apoptosis of WT EPCs. The present findings indicate that oxLDL disrupts the PI3K/Akt signaling pathway at the level of p85 in EPCs. This dysfunction can be reversed by ex vivo antioxidant therapy.

Duke Scholars

Published In

J Vasc Res

DOI

EISSN

1423-0135

Publication Date

2010

Volume

47

Issue

6

Start / End Page

519 / 530

Location

Switzerland

Related Subject Headings

  • Transfection
  • Time Factors
  • Superoxides
  • Stem Cells
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Oxidative Stress
  • Mutation
  • Mice, Knockout
 

Citation

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MLA
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Tie, G., Yan, J., Yang, Y., Park, B. D., Messina, J. A., Raffai, R. L., … Messina, L. M. (2010). Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res, 47(6), 519–530. https://doi.org/10.1159/000313879
Tie, Guodong, Jinglian Yan, Yagai Yang, Brian D. Park, Julia A. Messina, Robert L. Raffai, Philip T. Nowicki, and Louis M. Messina. “Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway.J Vasc Res 47, no. 6 (2010): 519–30. https://doi.org/10.1159/000313879.
Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, et al. Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res. 2010;47(6):519–30.
Tie, Guodong, et al. “Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway.J Vasc Res, vol. 47, no. 6, 2010, pp. 519–30. Pubmed, doi:10.1159/000313879.
Tie G, Yan J, Yang Y, Park BD, Messina JA, Raffai RL, Nowicki PT, Messina LM. Oxidized low-density lipoprotein induces apoptosis in endothelial progenitor cells by inactivating the phosphoinositide 3-kinase/Akt pathway. J Vasc Res. 2010;47(6):519–530.
Journal cover image

Published In

J Vasc Res

DOI

EISSN

1423-0135

Publication Date

2010

Volume

47

Issue

6

Start / End Page

519 / 530

Location

Switzerland

Related Subject Headings

  • Transfection
  • Time Factors
  • Superoxides
  • Stem Cells
  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Oxidative Stress
  • Mutation
  • Mice, Knockout