Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.
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.
White
Donald E
DE
Department of Biochemistry and Department of Medicine, McGill University, Montreal, Canada H3A 1A1.
Coutu
Pierre
P
Shi
Yan-Fen
YF
Tardif
Jean-Claude
JC
Nattel
Stanley
S
St Arnaud
René
R
Dedhar
Shoukat
S
Muller
William J
WJ
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
D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK