Basic Research in Cardiology

, Volume 104, Issue 5, pp 613–620

Role of extracellular signal-regulated kinase for endothelial progenitor cell dysfunction in coronary artery disease

  • Erik B. Friedrich
  • Christian Werner
  • Katrin Walenta
  • Michael Böhm
  • Bruno Scheller
Original Contribution

DOI: 10.1007/s00395-009-0022-6

Cite this article as:
Friedrich, E.B., Werner, C., Walenta, K. et al. Basic Res Cardiol (2009) 104: 613. doi:10.1007/s00395-009-0022-6

Abstract

In patients with coronary artery disease (CAD), number and function of endothelial progenitor cells (EPCs) are down-regulated. The relevant intracellular signalling mechanisms responsible for dysfunction of EPCs in CAD remain poorly characterized. Our goal was to examine the regulation of ERK-1/2 by SDF-1 and the role of ERK-1/2 for adhesion in EPCs. Western analysis revealed that the chemokine SDF-1 (SDF-1, 100 nM) mediates phosphorylation of ERK-2 after 90 s with a maximum after 180–300 s in EPCs isolated from healthy control subjects, while EPCs from patients with CAD are characterized by a temporally delayed and quantitatively markedly attenuated SDF-1-triggered ERK-2-phosphorylation. Functionally, EPCs isolated from patients with CAD display reduced SDF-1-induced adhesion under flow conditions, while augmenting ERK-2 signalling using an activating MEK-2 cDNA construct restores adhesion to control levels and rescues the adhesion defect of CAD-EPCs. These data indicate that defects in SDF-1-triggered EPC-adhesion contribute to the functional impairment of EPCs in CAD, and that ERK-2 represents a new therapeutic target for functional improvement of EPC adhesion in CAD.

Keywords

Extracellular signal-regulated kinaseEndothelial progenitor cellsStromal-derived factor-1AdhesionCoronary artery disease

Supplementary material

395_2009_22_MOESM1_ESM.doc (44 kb)
Supplementary material 1 (DOC 44 kb)
395_2009_22_MOESM2_ESM.ppt (10.4 mb)
Supplementary material 2 (PPT 10670 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Erik B. Friedrich
    • 1
  • Christian Werner
    • 1
  • Katrin Walenta
    • 1
  • Michael Böhm
    • 1
  • Bruno Scheller
    • 1
  1. 1.Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin)Universitätsklinikum des SaarlandesHomburg, SaarGermany