Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease.
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(+)/VEGFR-2(+), 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.
Werner
Christian
C
Klinik für Innere Medizin III-Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Böhm
Michael
M
Klinik für Innere Medizin III-Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Friedrich
Erik B
EB
Klinik für Innere Medizin III-Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany. Electronic address: efriedrich@med-in.uni-saarland.de.
D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000473:pathology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000201:enzymology / Q000473:pathology / Q000502:physiology*; D053668:Syndecan-1 / Q000378:metabolism; D000099200:Scaffold Protein ILK
D017346:Protein Serine-Threonine Kinases; D053668:Syndecan-1; D000099200:Scaffold Protein ILK; C508241:SDC1 protein, human