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

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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.

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Acknowledgments

This study was supported by the Deutsche Forschungsgemeinschaft (KFO 196) and a HOMFOR grant of the University of the Saarland. The excellent technical work of Bianca Werner and Claudia Schormann is greatly appreciated.

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  1. Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, 66421, Homburg, Saar, Germany

    Erik B. Friedrich, Christian Werner, Katrin Walenta, Michael Böhm & Bruno Scheller

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  1. Erik B. Friedrich
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  2. Christian Werner
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  4. Michael Böhm
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Correspondence to Erik B. Friedrich.

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Friedrich, E.B., Werner, C., Walenta, K. et al. Role of extracellular signal-regulated kinase for endothelial progenitor cell dysfunction in coronary artery disease. Basic Res Cardiol 104, 613–620 (2009). https://doi.org/10.1007/s00395-009-0022-6

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  • DOI: https://doi.org/10.1007/s00395-009-0022-6

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