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Cell Physiol Biochem. 2017;44(1):215-228. doi: 10.1159/000484648. Epub 2017 Nov 9.

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.

Author information

1
Department of Cardiology, the First Affiliated Hospital of China Medical University, Shenyang, China.
2
Department of Thoracic Surgery, the First Affiliated Hospital of China Medical University, Shenyang, China.
3
Department of Cardiology, the 2nd Affiliated Hospital of Harbin Medical University, Heilongjiang, China.
4
The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, China.

Abstract

BACKGROUND/AIMS:

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of vascular lesions, such as atherosclerosis and restenosis. PDGF-ββ, 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-ββ-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-ββ-treated VSMCs. We demonstrated that atorvastatin calcium induced cell cycle arrest in the G0/G1 phase in response to PDGF-ββ 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-ββ-treated VSMCs. Moreover, pretreatment with atorvastatin calcium inhibited the PDGF-ββ-treated phosphorylation of PDGFRβ and Akt, whereas atorvastatin calcium did not affect the phosphorylation of PLC-γ1 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 PDGFRβ-Akt signaling cascade.

KEYWORDS:

Akt; Atorvastatin calcium; PDGF-ββ; Vascular smooth muscle cells

PMID:
29131001
DOI:
10.1159/000484648
[Indexed for MEDLINE]
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