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Title: Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease

Abstract

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.

Authors:
;  [1]
  1. Klinik fuer Innere Medizin III-Kardiologie, Angiologie, Internistische Intensivmedizin, Universitaetsklinikum des Saarlandes, 66421 Homburg/Saar (Germany)
Publication Date:
OSTI Identifier:
21255772
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 377; Journal 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); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; BIOLOGICAL RECOVERY; CAPACITY; CELL PROLIFERATION; COLONY FORMING UNITS; CORONARIES; DISEASES; ENDOTHELIUM; HUMAN POPULATIONS; MIGRATION; PATIENTS; PHOSPHOTRANSFERASES; PROTEINS

Citation Formats

Werner, Christian, Boehm, Michael, and Friedrich, Erik B. Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.09.081.
Werner, Christian, Boehm, Michael, & Friedrich, Erik B. Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease. United States. https://doi.org/10.1016/j.bbrc.2008.09.081
Werner, Christian, Boehm, Michael, and Friedrich, Erik B. Fri . "Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease". United States. https://doi.org/10.1016/j.bbrc.2008.09.081.
@article{osti_21255772,
title = {Role of integrin-linked kinase for functional capacity of endothelial progenitor cells in patients with stable coronary artery disease},
author = {Werner, Christian and Boehm, Michael and Friedrich, Erik B.},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2008.09.081},
url = {https://www.osti.gov/biblio/21255772}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 377,
place = {United States},
year = {2008},
month = {12}
}