title: Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.
abstract: A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of integrin-associated genes in the murine heart. Here we show that targeted ablation of the integrin-linked kinase (ILK) expression results in spontaneous cardiomyopathy and heart failure by 6 wk of age. Deletion of ILK results in disaggregation of cardiomyocytes, associated with disruption of adhesion signaling through the beta1-integrin/FAK (focal adhesion kinase) complex. Importantly, the loss of ILK is accompanied by a reduction in cardiac Akt phosphorylation, which normally provides a protective response against stress. Together, these results suggest that ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure.
authors.affiliation: Department of Biochemistry and Department of Medicine, McGill University, Montreal, Canada H3A 1A1.
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Pierre
authors.initials: P
authors.lastname: Coutu
authors.forename: Yan-Fen
authors.initials: YF
authors.lastname: Shi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
authors.forename: René
authors.initials: R
authors.lastname: St Arnaud
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
authors.forename: William J
authors.initials: WJ
authors.lastname: Muller
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000201:enzymology / Q000235:genetics*; D003645:Death, Sudden; D018390:Gene Targeting; D006333:Heart Failure / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics*; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK