Rosuvastatin suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation and migration via the MAPK signaling pathway
| Autor: | Jianting Gan, Ruixing Yin, Zhengdong Wang, Ping Li, Wenchao Xie, Ming Liu, Feng Huang, Xiangwen Liang, Jian Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Cancer Research Platelet-derived growth factor Vascular smooth muscle mitogen-activated protein kinase proliferation p38 mitogen-activated protein kinases Pharmacology migration platelet-derived growth factor chemistry.chemical_compound Immunology and Microbiology (miscellaneous) Medicine Rosuvastatin Protein kinase A biology business.industry nutritional and metabolic diseases Articles General Medicine chemistry Mitogen-activated protein kinase biology.protein vascular smooth muscle cell Signal transduction business rosuvastatin medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2013.1265 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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