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.

Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling

“…In addition, PDGF-BB has been reported to play a stimulatory role in the regulation of this phenotype switch (19,20). Accordingly, the effect of AS-IV on the PDGF-BB-stimulated phenotype switch of HDVSMCs was further investigated.…”

Death-associated protein kinase 3 mediates vascular structural remodelling via stimulating smooth muscle cell proliferation and migration

“…Effects of DAPK3 gene knockdown on PDGF-BB-activated intracellular signalling p38 [19], HSP27 [20], Akt [21] and ERK [19] are known as the intracellular signalling molecules involved in SMC proliferation and migration. We, therefore, investigated the effects of DAPK3 gene knockdown on PDGF-BB (10 ng/ml, 20 min)-induced phosphorylation of these molecules.…”

Involvement of MicroRNA-133a in the Development of Arteriosclerosis Obliterans of the Lower Extremities via RhoA Targeting

“…Then, the quiescent cells were stimulated into a proliferating state by PDGF-BB 12) . As a result, the miR-133a expression was significantly downregulated in the proliferating HASMCs, especially at eight hours after PDGF-BB stimulation, compared to that observed in the quiescent cells (P 0.05) (Fig.…”