Zinc alleviates vascular calcification by activating ERK1/2-mediated autophagy

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.