title: Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway.
abstract: An imbalance in the proliferation and migration of vascular smooth muscle cells (VSMCs) is significant in the onset and progression of vascular diseases, including arteriosclerosis and restenosis subsequent to vein grafting or coronary intervention. Rosuvastatin, a selective inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, has pharmacological properties including the ability to reduce low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) levels, slow atherosclerosis progression and improve coronary heart disease outcomes. However, little is known concerning the molecular mechanism by which rosuvastatin affects vascular cell dynamics. In this study, we studied the inhibitory role of rosuvastatin on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, as well as the molecular mechanisms involved. MTT data showed that rosuvastatin markedly inhibited the proliferation of PDGF-BB-induced VSMCs in a time-dependent manner. VSMCs are able to dedifferentiate into a proliferative phenotype in response to PDGF-BB stimulation; however, rosuvastatin effectively attenuated this phenotype switching. Moreover, we also showed that rosuvastatin significantly suppressed PDGF-BB-induced VSMC migration, which may be a result of its inhibitory effect on the protein expression of matrix metalloproteinase-2 (MMP2) and MMP9. Investigation into the molecular mechanisms involved revealed that rosuvastatin inhibited the mitogen-activated protein kinase (MAPK) signaling pathway by downregulating extracellular signal-regulated kinase (ERK) and p38 MAPK, although the phosphorylation level of c-Jun N-terminal kinase (c-JNK) was not altered following rosuvastatin treatment. In conclusion, the present study showed that rosuvastatin suppressed PDGF-BB-induced VSMC proliferation and migration, indicating that rosuvastatin has the potential to become a promising therapeutic agent for the treatment of atherosclerosis and restenosis.
authors.affiliation: Department of Cardiology, Sixth Affiliated Hospital of Guangxi Medical University, Yulin, Guangxi 537000;
authors.forename: Jianting
authors.initials: J
authors.lastname: Gan
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Wenchao
authors.initials: W
authors.lastname: Xie
authors.forename: Ruixing
authors.initials: R
authors.lastname: Yin
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
keywords: migration; mitogen-activated protein kinase; platelet-derived growth factor; proliferation; rosuvastatin; vascular smooth muscle cell