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Journal of cellular and molecular medicine
12, 2020;24 (23): 13648-13659.

Aldosterone enhances high phosphate-induced vascular calcification through inhibition of AMPK-mediated autophagy.

Jing-Wei Gao, Wan-Bing He, Chang-Ming Xie, Ming Gao, Lei-Yu Feng, Zhao-Yu Liu, Jing-Feng Wang, Hui Huang, Pin-Ming Liu
Author Information
  1. Jing-Wei Gao: Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
  2. Wan-Bing He: Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
  3. Chang-Ming Xie: Cardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
  4. Ming Gao: Department of Radiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
  5. Lei-Yu Feng: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  6. Zhao-Yu Liu: Medical Research Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
  7. Jing-Feng Wang: Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
  8. Hui Huang: Cardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. ORCID
  9. Pin-Ming Liu: Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China. ORCID
PMID: 33150736 DOI: 10.1111/jcmm.15813

Abstract

It remains unclear whether the necessity of calcified mellitus induced by high inorganic phosphate (Pi) is required and the roles of autophagy plays in aldosterone (Aldo)-enhanced vascular calcification (VC) and vascular smooth muscle cell (VSMC) osteogenic differentiation. In the present study, we found that Aldo enhanced VC both in vivo and in vitro only in the presence of high Pi, alongside with increased expression of VSMC osteogenic proteins (BMP2, Runx2 and OCN) and decreased expression of VSMC contractile proteins (α-SMA, SM22α and smoothelin). However, these effects were blocked by mineralocorticoid receptor inhibitor, spironolactone. In addition, the stimulatory effects of Aldo on VSMC calcification were further accelerated by the autophagy inhibitor, 3-MA, and were counteracted by the autophagy inducer, rapamycin. Moreover, inhibiting adenosine monophosphate-activated protein kinase (AMPK) by Compound C attenuated Aldo/MR-enhanced VC. These results suggested that Aldo facilitates high Pi-induced VSMC osteogenic phenotypic switch and calcification through MR-mediated signalling pathways that involve AMPK-dependent autophagy, which provided new insights into Aldo excess-associated VC in various settings.

Keywords

aldosterone autophagy phenotypic switch vascular calcification vascular smooth muscle cell

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MeSH Term

AMP-Activated Protein Kinases
Aldosterone
Animals
Autophagy
Biomarkers
Calcium
Cell Differentiation
Cells, Cultured
Female
Gene Expression
Genes, Reporter
Mice
Models, Biological
Osteogenesis
Phosphates
Signal Transduction
Vascular Calcification

Chemicals

Biomarkers
Phosphates
Aldosterone
AMP-Activated Protein Kinases
Calcium
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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