Role of integrin-linked kinase in vascular smooth muscle cells: regulation by statins and angiotensin II |
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Authors: | Friedrich Erik B Clever Yvonne P Wassmann Sven Werner Nikos Böhm Michael Nickenig Georg |
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Institution: | Klinik für Innere Medizin III Kardiologie, Angiologie, Internistische Intensivmedizin, Universit?tskliniken des Saarlandes, 66421 Homburg/Saar, Germany. efriedrich@med-in.uni-sb.de |
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Abstract: | 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. |
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Keywords: | Integrin-linked kinase Vascular smooth muscle cells Statins Angiotensin II Atherosclerosis |
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