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Zinc alleviates vascular calcification by activating ERK1/2-mediated autophagy
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Zinc alleviates vascular calcification by activating ERK1/2-mediated autophagy
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Journal Article
Zinc alleviates vascular calcification by activating ERK1/2-mediated autophagy
2025
Overview
Chronic kidney disease (CKD) causes a significant health and economic burden across the world. This study aimed to evaluate the effects of zinc on CKD-mineral bone disorder (CKD-MBD) and autophagy in CKD rats by a diet containing 0.25% adenine and low vitamin K and to explore its mechanism of action on autophagy and calcification in a vascular smooth muscle cell (VSMC) calcification model using 10 mM β-glycerophosphate (β-GP). In vivo experiments showed that zinc supplementation improved blood and urinary biochemistry, corrected abnormalities related to bone metabolism in rats with CKD, promoted autophagy, and reduced aortic calcification. In vitro, zinc reduced the calcification of VSMCs induced by β-GP. During VSMC calcification, zinc further upregulated autophagy levels and the phosphorylated extracellular regulatory kinase1/2 (ERK1/2) levels in a high-phosphorus environment. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, or with U0126, an ERK1/2 pathway inhibitor, decreased autophagy and increased calcification. In conclusion, zinc improved CKD-MBD by inhibiting vascular calcification (VC) and ameliorating bone metabolism disorders. Furthermore, zinc alleviates VC in CKD by activating ERK1/2-mediated autophagy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adenine
/ Animals
/ ERK1/2
/ Extracellular signal-regulated kinase
/ Humanities and Social Sciences
/ Male
/ MAP Kinase Signaling System - drug effects
/ Minerals
/ Muscle, Smooth, Vascular - drug effects
/ Muscle, Smooth, Vascular - metabolism
/ Muscle, Smooth, Vascular - pathology
/ Myocytes, Smooth Muscle - drug effects
/ Myocytes, Smooth Muscle - metabolism
/ Proteins
/ Rats
/ Renal Insufficiency, Chronic - complications
/ Renal Insufficiency, Chronic - drug therapy
/ Renal Insufficiency, Chronic - metabolism
/ Science
/ Vascular Calcification - drug therapy
/ Vascular Calcification - metabolism
/ Vascular Calcification - pathology
/ Zinc
