溴结构域蛋白4抑制剂JQ1在血管钙化中的作用及机制研究OA

Objective To investigate the expression of bromodomain-containing protein 4(BRD4)in vascular calcification,to evaluate the effect of its inhibitor JQ1 on vascular calcification,and to explore the underlying mechanisms.Methods Vascular smooth muscle cells(VSMCs)isolated from rats were cultured under high-phosphate conditions to induce calcification and then treated with JQ1.Calcification of the VSMCs was assessed via calcium content determination,Alizarin Red staining,and von Kossa staining.Protein expression levels of BRD4,RUNX2,and ACSL4 were determined by Western blot.The acute aortic calcification was induced in C57BL/6J mice through subcutaneous injection of VD3,followed by intraperitoneal injection of JQ1.Aortic calcification of mice was evaluated through calcium content determination and Alizarin Red staining,and protein expression levels of BRD4 and RUNX2 were detected by Western blot.The effect of JQ1 on BRD4 enrichment at the ACSL4 promoter region was analyzed using published ChIP-seq data from the NCBI database.Results BRD4 expression was significantly upregulated in calcified VSMCs.JQ1 significantly alleviated vascular calcification both in vivo and in vitro,and downregulated the expression of BRD4 and RUNX2.Moreover,JQ1 significantly reduced BRD4 enrichment at the promoter region of ACSL4,thereby inhibiting ACSL4 transcriptional activity.Conclusion JQ1 inhibits vascular calcification.This effect may be mediated by downregulation of BRD4 expression,which subsequently reduces ACSL4 transcriptional activity and ultimately inhibits ferroptosis in VSMCs.