1. Academic Validation
  2. Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification

Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification

  • Mol Cell Biochem. 2020 Aug;471(1-2):91-100. doi: 10.1007/s11010-020-03769-9.
Yanyan Liu 1 Jing Li 2 Yuting Han 1 Yuying Chen 1 Lixuan Liu 1 Jiangli Lang 1 Chuan Yang 1 Hengcong Luo 3 Jie Ning 4
Affiliations

Affiliations

  • 1 Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.
  • 2 Department of Endocrinology, The Third Affiliated Hospital, Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, 510150, China.
  • 3 Department of Endocrinology, The Third Affiliated Hospital, Guangzhou Medical University, 63 Duobao Road, Liwan District, Guangzhou, 510150, China. 406721077@qq.com.
  • 4 Department of Endocrinology, Shenzhen Longhua District Central Hospital, Guangdong Medical University Affiliated Longhua Central Hospital, Shenzhen, 518110, Guangdong, China. 406721077@qq.com.
Abstract

Vascular calcification is closely linked to patients in diabetes mellitus and chronic kidney disease. Advanced glycation end-products (AGEs) are associated with osteogenic differentiation of vascular smooth muscle cell (VSMC), vascular calcification, and Autophagy that takes part in the process. However, the underlying mechanism of the effects of AGEs on the phenotypic transition and Autophagy of VSMCs is not clearly understood. In this study, we cultured the rat VSMC line (A7R5) and thoracic aorta organ with bovine serum albumin (BSA) or AGEs (AGEs-BSA) and detected proteins expression by Western blotting or immunofluorescence. Autophagosome was observed by transmission electron microscopy (TEM). The mineralization and calcific nodules were identified by Alizarin Red S and Von Kossa staining. AGEs significantly downregulated p-AMPKα expression and upregulated p-mTOR expression and then increased the expression of osteoblastic differentiation, while suppressing Autophagy in a time-dependent pattern. Pretreatment with Autophagy activator rapamycin and AMPK Activator AICAR both upregulated the Autophagy level and downregulated the effects of AGEs on osteoblastic differentiation of VSMCs. Moreover, the result from rat thoracic aorta culture also confirmed that AGEs promote vascular calcification in a time-dependent manner. Thus, our study showed that AGEs quicken vascular calcification and suppress Autophagy associated with AMPK/mTOR signaling pathway.

Keywords

AMPK/mTOR; Advanced glycation end-products; Autophagy; Osteoblastic differentiation; Vascular calcification; Vascular smooth muscle cell.

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