Atorvastatin Protects Vascular Smooth Muscle Cells From TGF-beta 1-Stimulated Calcification by Inducing Autophagy via Suppression of the beta-Catenin Pathway

作者：Liu Demin; Cui Wei^*; Liu Bin; Hu Haijuan; Liu Jing; Xie Ruiqin; Yang Xiaohong; Gu Guoqiang; Zhang Jidong; Zheng Hongmei

来源：Cellular Physiology and Biochemistry, 2014, 33(1): 129-141.

DOI：10.1159/000356656

• Atorvastatin
• autophagy
• beta-catenin
• Calcification
• TGF-beta 1
• VSMCs

Background: Arterial calcification is a major event in the progression of atherosclerosis. It is reported that statins exhibit various protective effects against vascular smooth muscle cell (VSMC) inflammation and proliferation in cardiovascular remodeling. Although statins counteract atherosclerosis, the molecular mechanisms of statins on the calcium release from VSMCs have not been clearly elucidated. Methods: Calcium content of VSMCs was measured using enzyme-linked immunosorbent assay (ELISA). The expression of proteins involved in cellular transdifferentiation was analyzed by western blot. Cell autophagy was measured by fluorescence microscopic analysis for acridine orange staining and transmission electron microscopy analysis. The autophagic inhibitors (3-MA, chloroquine, NH4Cl and bafilomycin A1) and beta-catenin inhibitor JW74 were used to assess the effects of atorvastatin on autophagy and the involvement of beta-catenin on cell calcification respectively. Furthermore, cell transfection was performed to overexpress beta-catenin. Results: In VSMCs, atorvastatin significantly suppressed transforming growth factor-beta 1 (TGF-beta 1)-stimulated calcification, accompanied by the induction of autophagy. Downregulation of autophagy with autophagic inhibitors significantly suppressed the inhibitory effect of atorvastatin on cell calcification. Moreover, the beneficial effect of atorvastatin on calcification and autophagy was reversed by beta-catenin overexpression. Conversely, JW74 supplement enhanced this effect. Conclusion: These data demonstrated that atorvastatin protect VSMC from TGF-beta 1-stimulated calcification by inducing autophagy through suppression of the beta-catenin pathway, identifying autophagy induction might be a therapeutic strategy for use in vascular calcification.

• 出版日期2014
• 单位河北医科大学