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Rosuvastatin regulates vascular smooth muscle cell phenotypic modulation in vascular remodeling: role for the urokinase receptor

Item Type:Article
Title:Rosuvastatin regulates vascular smooth muscle cell phenotypic modulation in vascular remodeling: role for the urokinase receptor
Creators Name:Kiyan, J. and Kusch, A. and Tkachuk, S. and Kraemer, J. and Haller, H. and Dietz, R. and Smith, G. and Dumler, I.
Abstract:The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of migration and proliferation of vascular smooth muscle cells (VSMC). However, whether uPA/uPAR-directed mechanisms are involved in the beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on vascular remodeling remains unexplored. In this study, we have investigated the effect of the hydrophilic statin rosuvastatin on neointimal remodeling, and the role of uPAR. Using an ex vivo organ and in vitro cell culture models we demonstrate that rosuvastatin decreases injury-induced neointima formation and proliferation of medial VSMC in porcine coronary arteries, as well as migration and proliferation of human coronary VSMC. Studies on the underlying mechanisms show that rosuvastatin impairs VSMC transition from their physiological contractile to the pathophysiologal synthetic phenotype. These effects are mediated, at least in part, via uPAR, as confirmed by means of rosuvastatin-directed uPAR expression and uPAR silencing in both models. Our findings provide evidence that rosuvastatin modulates VSMC phenotypic changes and subsequently their proliferation and migration, and indicate the important role for uPAR in these processes. This mechanism contributes to the beneficial non-lipid lowering effect of rosuvastatin on negative vascular remodeling.
Keywords:Rosuvastatin, Urokinase Receptor, Vascular Smooth Muscle Cell, Cell Phenotypic Modulation, Vascular Remodeling, Animals, Sus Scrofa
Source:Atherosclerosis
ISSN:0021-9150
Publisher:Elsevier (The Netherlands)
Volume:195
Number:2
Page Range:254-261
Date:December 2007
Official Publication:https://doi.org/10.1016/j.atherosclerosis.2006.12.030
PubMed:View item in PubMed

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