Atorvastatin Calcium Inhibits PDGF-ββ-Induced Proliferation and Migration of VSMCs Through the G0/G1 Cell Cycle Arrest and Suppression of Activated PDGFRβ-PI3K-Akt Signaling Cascade

被引：24

作者：

Chen, Shuang ^{[1
]}

Dong, Siyuan ^{[2
]}

Li, Zhao ^{[1
]}

Guo, Xiaofan ^{[1
]}

Zhang, Naijin ^{[1
]}

Yu, Bo ^{[3
,4
]}

Sun, Yingxian ^{[1
]}

机构：

[1] China Med Univ, Dept Cardiol, Affiliated Hosp 1, Shenyang, Liaoning, Peoples R China

[2] China Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Shenyang, Liaoning, Peoples R China

[3] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Heilongjiang, Peoples R China

[4] Harbin Med Univ, Key Lab Myocardial Ischemia, Minist Educ, Harbin, Heilongjiang, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 44卷 / 01期

关键词：

Vascular smooth muscle cells; PDGF-beta beta; Atorvastatin calcium; Akt; VASCULAR SMOOTH-MUSCLE; GROWTH-FACTOR; NEOINTIMAL HYPERPLASIA; TRANSDUCTION PATHWAYS; INTIMAL HYPERPLASIA; PORCINE CORONARY; ATHEROSCLEROSIS; INJURY; PROGRESSION; PROTEIN;

D O I：

10.1159/000484648

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular lesions, such as atherosclerosis and restenosis. PDGF-beta beta, an isoform of PDGF (platelet-derived growth factor), has been demonstrated to induce proliferation and migration of VSMCs. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has favorable protective effects on VSMCs. This study examined the effects of atorvastatin calcium on the proliferation and migration of PDGF-beta beta-treated VSMCs, as well as its underlying mechanisms. Methods: MTT assays, Edu imaging, cell cycle analysis, wound healing assays, transwell migration assays, and western blot analysis were performed. Results: Atorvastatin calcium significantly inhibited cell proliferation, DNA synthesis and cell migration of PDGF-beta beta-treated VSMCs. We demonstrated that atorvastatin calcium induced cell cycle arrest in the G0/G1 phase in response to PDGF-beta beta stimulation and decreased the expression of G0/G1-specific regulatory proteins, including proliferating cell nuclear antigen (PCNA), CDK2, cyclin D1, cyclin E and CDK4 in PDGF-beta beta-treated VSMCs. Moreover, pretreatment with atorvastatin calcium inhibited the PDGF-beta beta-treated phosphorylation of PDGFR beta and Akt, whereas atorvastatin calcium did not affect the phosphorylation of PLC-gamma 1 or (ERK) 1/2. Conclusion: Our data suggested that atorvastatin calcium inhibited abnormal proliferation and migration of VSMCs through G0/G1 cell cycle arrest and suppression of the PDGFR beta-Akt signaling cascade. (c) 2017 The Author(s) Published by S. Karger AG, Basel

引用

页码：215 / 228

页数：14

共 49 条

[31]

2-I

[32]

Owens GK, 1997, AGENT ACTION SUPPL, V48, P3

[33] Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration [J].

Porter, KE ;

Naik, J ;

Turner, NA ;

Dickinson, T ;

Thompson, MM ;

London, NJM .

JOURNAL OF VASCULAR SURGERY, 2002, 36 (01) :150-157

[34]

Pyles JM, 1997, CIRC RES, V81, P904

[35] PDGF and cardiovascular disease [J].

Raines, EW .

CYTOKINE & GROWTH FACTOR REVIEWS, 2004, 15 (04) :237-254

[36]

Ross R, 1990, Adv Nephrol Necker Hosp, V19, P79

[37] THE PATHOGENESIS OF ATHEROSCLEROSIS - A PERSPECTIVE FOR THE 1990S [J].

ROSS, R .

NATURE, 1993, 362 (6423) :801-809

[38] Regulation of vascular smooth muscle cell differentiation [J].

Rzucidlo, Eva M. ;

Martin, Kathleen A. ;

Powell, Richard J. .

JOURNAL OF VASCULAR SURGERY, 2007, 45 :25A-32A

[39]

SACHINIDIS A, 1990, J BIOL CHEM, V265, P10238

[40]

SASAGURI Y, 1994, LAB INVEST, V71, P261

← 1 2 3 4 5 →