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Basic Research in Cardiology

Erschienen in:

01.09.2009 | Original Contribution

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

verfasst von: Erik B. Friedrich, Christian Werner, Katrin Walenta, Michael Böhm, Bruno Scheller

Erschienen in: Basic Research in Cardiology | Ausgabe 5/2009

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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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Titel: Role of extracellular signal-regulated kinase for endothelial progenitor cell dysfunction in coronary artery disease
verfasst von: Erik B. Friedrich
Christian Werner
Katrin Walenta
Michael Böhm
Bruno Scheller
Publikationsdatum: 01.09.2009
Verlag: D. Steinkopff-Verlag
Erschienen in: Basic Research in Cardiology / Ausgabe 5/2009
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-009-0022-6

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