Role of integrin-linked kinase in vascular smooth muscle cells: regulation by statins and angiotensin II.
Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular smooth muscle cells (VSMC), which play a crucial role in atherogenesis. Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs revealed that ILK mediates migration and proliferation of VSMC but has no effect on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK protein expression and kinase activity while statin treatment down-regulates ILK in VSMC. Functionally, ILK is necessary for angiotensin II-mediated VSMC migration and proliferation. In VSMC transduced with dominant-negative ILK, statins mediate an additive inhibition of VSMC migration and proliferation, while transfection with wild-type ILK is sufficient to overcome the inhibitory effects of statin treatment on VSMC migration and proliferation. In vivo, ILK is expressed in VSMC of aortic sections from wild-type mice where it is down-regulated following statin treatment and up-regulated following induction of atherosclerosis in apoE-/- mice. These data identify ILK as a novel target in VSMC for anti-atherosclerotic therapy.
Friedrich
Erik B
EB
Klinik für Innere Medizin III Kardiologie, Angiologie, Internistische Intensivmedizin, Universitätskliniken des Saarlandes, 66421 Homburg/Saar, Germany. efriedrich@med-in.uni-sb.de
Clever
Yvonne P
YP
Wassmann
Sven
S
Werner
Nikos
N
Böhm
Michael
M
Nickenig
Georg
G
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D000099200:Scaffold Protein ILK
D000804:Angiotensin II; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK