title: Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.
abstract: 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.
authors: Department of Cardiology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
authors: Shuang
authors: S
authors: Chen
authors: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang Liaoning, China.
authors: Baoqin
authors: B
authors: Liu
authors: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang Liaoning, China.
authors: Dehui
authors: D
authors: Kong
authors: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang Liaoning, China.
authors: Si
authors: S
authors: Li
authors: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang Liaoning, China.
authors: Chao
authors: C
authors: Li
authors: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang Liaoning, China.
authors: Huaqin
authors: H
authors: Wang
authors: Department of Cardiology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
authors: Yingxian
authors: Y
authors: Sun
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D000077214:Becaplermin; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D004247:DNA; D000069059:Atorvastatin; D051057:Proto-Oncogene Proteins c-akt