title: 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.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
authors.forename: Stephanie I
authors.initials: SI
authors.lastname: Bettink
authors.forename: Christian
authors.initials: C
authors.lastname: Werner
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chen
authors.forename: Patrick
authors.initials: P
authors.lastname: Müller
authors.forename: Stephan H
authors.initials: SH
authors.lastname: Schirmer
authors.forename: Katrin L
authors.initials: KL
authors.lastname: Walenta
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.forename: Erik B
authors.initials: EB
authors.lastname: Friedrich
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D054377:Chemokine CXCL12; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D019718:Receptors, CXCR4; D020830:rac1 GTP-Binding Protein; D000099200:Scaffold Protein ILK; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human