Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway

Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high...

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Published in:	PloS one 2015-04, Vol.10 (4), p.e0122577-e0122577
Main Authors:	Chen, Shuang, Liu, Baoqin, Kong, Dehui, Li, Si, Li, Chao, Wang, Huaqin, Sun, Yingxian
Format:	Article
Language:	eng
Subjects:	Actin Actin Cytoskeleton - drug effects Actin Cytoskeleton - metabolism Activation AKT protein Animals Antilipemic agents Atorvastatin Atorvastatin - pharmacology Becaplermin Blotting, Western Calcium Calponin Cell Movement - drug effects Cell Proliferation - drug effects Cell Shape - drug effects Cells, Cultured Cellular signal transduction Coenzyme A Cytoskeleton Cytoskeleton - drug effects Cytoskeleton - metabolism DNA - biosynthesis DNA - genetics Dose-Response Relationship, Drug Down-Regulation - drug effects Enzymes Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Inhibition Male Microscopy, Confocal Modulation Muscle contraction Muscle proteins Muscle, Smooth, Vascular - cytology Muscles Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Phenotypic plasticity Phosphorylation Platelet-derived growth factor Platelet-derived growth factor BB Proteins Proto-Oncogene Proteins c-akt - metabolism Proto-Oncogene Proteins c-sis - pharmacology Rats, Sprague-Dawley Reductase Secretion Signal transduction Signal Transduction - drug effects Signaling Smooth muscle Time Factors Vascular diseases
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Summary:	Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.
ISSN:	1932-6203 1932-6203