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

Molecular and Cellular Biochemistry
Yanyan LiuJie Ning

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 aor...Continue Reading

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Citations

Dec 2, 2020·International Journal of Molecular Sciences·Cédric H G NeutelPieter-Jan Guns
Jan 29, 2021·Journal of Biochemical and Molecular Toxicology·C R Sruthi, K G Raghu
May 29, 2021·Frontiers in Cardiovascular Medicine·Yi LuZhejun Cai
Jun 8, 2021·Oxidative Medicine and Cellular Longevity·Shiyu SongLi Kong

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Methods Mentioned

BETA
Protein Assay
transmission electron microscopy

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