Heart and Vessels

, Volume 30, Issue 1, pp 115–125

Impact of lysophosphatidylcholine on survival and function of UEA-1+acLDL+ endothelial progenitor cells in patients with coronary artery disease

  • Seong Hun Hong
  • Hyun Hee Jang
  • So Ra Lee
  • Kyung Hye Lee
  • Jong Shin Woo
  • Jin Bae Kim
  • Woo-Shik Kim
  • Byung Il Min
  • Ki Ho Cho
  • Kwon Sam Kim
  • Xianwu Cheng
  • Weon Kim
Original Article

DOI: 10.1007/s00380-014-0473-z

Cite this article as:
Hong, S.H., Jang, H.H., Lee, S.R. et al. Heart Vessels (2015) 30: 115. doi:10.1007/s00380-014-0473-z

Abstract

Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1+acLDL+ EPCs). UEA-1+acLDL+ EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40 μM). UEA-1+acLDL+ EPCs were preincubated for 30 min with pravastatin (20 μM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 μM. The survival, migration, adhesion, and proliferation of UEA-1+acLDL+ EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1+acLDL+ EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1+acLDL+ EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1+acLDL+ EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization.

Keywords

Lysophosphatidylcholine Endothelial progenitor cell Pravastatin Coronary artery disease Vulnerable plaque 

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Seong Hun Hong
    • 1
  • Hyun Hee Jang
    • 1
  • So Ra Lee
    • 1
  • Kyung Hye Lee
    • 1
  • Jong Shin Woo
    • 1
  • Jin Bae Kim
    • 1
  • Woo-Shik Kim
    • 1
  • Byung Il Min
    • 2
    • 3
  • Ki Ho Cho
    • 4
  • Kwon Sam Kim
    • 1
  • Xianwu Cheng
    • 5
  • Weon Kim
    • 1
    • 2
  1. 1.Division of CardiologyKyung Hee UniversitySeoulRepublic of Korea
  2. 2.Cardiovascular Division, Department of Internal Medicine, Kyung Hee University HospitalKyung Hee UniversitySeoulRepublic of Korea
  3. 3.Department of PhysiologyKyung Hee UniversitySeoulRepublic of Korea
  4. 4.Department of Cardiovascular and Neurologic DiseaseHospital of Korean MedicineSeoulRepublic of Korea
  5. 5.Nagoya University Graduate School of MedicineNagoyaJapan