Enhancer of Zeste Homologue 2 Promotes Vascular Calcification Associated With Chronic Kidney Disease

BACKGROUND: As a predominant complication of chronic kidney disease (CKD), vascular calcification (VC) warrants investigation into its mechanisms. The epigenetic modulator Enhancer of Zeste Homologue 2 (EZH2) is implicated in various kidney disorders. This investigation aims to examine its function in the development of VC related to CKD. METHODS: model of calcification was established by treating A7r5, a rat vascular smooth muscle cell line (VSMC), with a calcifying medium, and 3-DZNeP was used to inhibit EZH2. Adenovirus was used to overexpress EZH2 and siRNA was used to silence bone morphogenetic protein (BMP) 2. RESULTS: , EZH2 and H3K27me3 were noticeably elevated in calcifying VSMCs. Mechanistically, overexpression of EZH2 aggravated the VSMCs' calcification through upregulation of BMP2. CONCLUSION: Our study demonstrated the elevated EZH2 expression in calcified vascular tissues from both CKD patients and preclinical models, including CKD mice, cultured rat aortas, and VSMCs calcification models. EZH2 may promote VC through activation of BMP2 signaling. Targeting EZH2 could be a therapeutic strategy against CKD associated VC.