Integrin-linked kinase is a central mediator in angiotensin II type 1- and chemokine receptor CXCR4 signaling in myocardial hypertrophy.

Abstract

Inflammation and pro-hypertrophic signaling are important for development and progression of myocardial hypertrophy (LVH) and chronic heart failure (CHF). Here we investigated the relevance of integrin-linked kinase (ILK) for chemokine receptor CXCR4- and angiotensin II type 1-triggered signaling and its regulation and role in cardiac remodeling. Using ELISA, real-time-PCR, and Western blotting, the present study demonstrates that SDF-1 and its receptor CXCR4 are up-regulated in plasma and left ventricles, respectively, in mouse models of cardiac hypertrophy (transaortic constriction, transgenic cardiac-specific overexpression of rac1) and in human CHF in association with increased cardiac ILK-expression. In isolated cardiomyocytes, ILK is activated by CXCR4-ligation and necessary for SDF-1-triggered activation of rac1, NAD(P)H oxidase, and release of reactive oxygen species. Importantly, the pro-hypertrophic peptide angiotensin II induces ILK-activation dependent on rac1 in cardiomyocytes, where ILK is necessary for angiotensin II-mediated stimulation of hypertrophy genes and protein synthesis. We conclude that in both SDF-1- and angiotensin II-triggered signaling, ILK is a central mediator of rac1-induced oxidative stress and myocardial hypertrophy.

• Authors: Stephanie I Bettink, Christian Werner, Chia-Hui Chen, Patrick Müller, Stephan H Schirmer, Katrin L Walenta, Michael Böhm, Ulrich Laufs, Erik B Friedrich
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 397 Issue 2 Pg. 208-13 (Jun 25 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20493167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• CXCL12 protein, human
• CXCR4 protein, human
• Chemokine CXCL12
• Reactive Oxygen Species
• Receptor, Angiotensin, Type 1
• Receptors, CXCR4
• integrin-linked kinase
• Protein Serine-Threonine Kinases
• rac1 GTP-Binding Protein

Topics

• Animals
• Cardiomegaly (metabolism)
• Cells, Cultured
• Chemokine CXCL12 (metabolism)
• Heart Failure (metabolism)
• Humans
• Mice
• Mice, Transgenic
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Receptor, Angiotensin, Type 1 (metabolism)
• Receptors, CXCR4 (metabolism)
• rac1 GTP-Binding Protein (metabolism)