Journal Article

Aldosterone enhances high phosphate–induced vascular calcification through inhibition of AMPK‐mediated autophagy

Liu, Pin‐Ming, Gao, Ming, Huang, Hui, He, Wan‐Bing, Liu, Zhao‐Yu, Gao, Jing‐Wei, Xie, Chang‐Ming, Wang, Jing‐Feng, Feng, Lei‐Yu

2020

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adenosine kinase / Adenoviruses / Aldosterone / Aldosterone - metabolism / Aldosterone - pharmacology / AMP / AMP-activated protein kinase / AMP-Activated Protein Kinases - metabolism / Animals / Antibodies / Autophagy / Autophagy - drug effects / Biomarkers / Calcification / Calcification (ectopic) / Calcium - metabolism / Cbfa-1 protein / Cell differentiation / Cell Differentiation - drug effects / Cells, Cultured / Experiments / Female / Gene Expression / Genes, Reporter / Homeostasis / Hypertension / Kinases / Laboratory animals / Membranes / Mice / Mineralocorticoid receptors / Models, Biological / Muscle contraction / Original / Osteogenesis - drug effects / Phagocytosis / phenotypic switch / Phosphates - metabolism / Phosphates - pharmacology / Phosphorus / Protein kinase / Proteins / Rapamycin / Signal transduction / Signal Transduction - drug effects / Smooth muscle / Statistical analysis / vascular calcification / Vascular Calcification - etiology / Vascular Calcification - metabolism / Vascular Calcification - pathology / vascular smooth muscle cell