Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease
- Klinik fuer Innere Medizin III-Kardiologie, Angiologie, Internistische Intensivmedizin, Universitaetsklinikum des Saarlandes, 66421 Homburg/Saar (Germany)
Number and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs. Human EPCs transduced with dominant-negative ILK (DN-ILK) display significantly reduced expression of CD34{sup +}/VEGFR-2{sup +}, DiI-Ac-LDL uptake, and Ulex europaeus lectin binding. Mechanistically, DN-ILK-transfected EPCs are characterized by decreased proliferation, while proliferation is increased in wild-type ILK-transfected EPCs. These effects are paralleled by changes in cyclin D1 expression, colony forming units, and cytoskeletal rearrangement. Functionally, ILK is necessary and sufficient for SDF-1-triggered migration and adhesion in EPCs. These data extend current knowledge about the role of ILK in EPC biology and implicate ILK as a therapeutic target in CAD.
- OSTI ID:
- 21255772
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 377, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.09.081; PII: S0006-291X(08)01830-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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