Role and mechanism of the bromodomain-containing protein 4 inhibitor JQ1 in vascular calcification

ZHAO Jun-yong; WANG Ze-lan; LUO Wen-jian; LUO Xiao-lin; LIU Xi; QIN Zhe-xue

doi:10.11659/jjssx.11E025040

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Role and mechanism of the bromodomain-containing protein 4 inhibitor JQ1 in vascular calcification

Basic Research | 更新时间：2026-03-17

- Role and mechanism of the bromodomain-containing protein 4 inhibitor JQ1 in vascular calcification
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 3, Pages: 226-231(2026)
- 作者机构：
  
  陆军军医大学第二附属医院心血管内科，重庆 400037
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.11E025040
  CLC： R543.1
- Received：06 November 2025，
  
  Published：25 March 2026
- 稿件说明：
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赵俊勇,王泽澜,罗稳健等.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[J].局解手术学杂志,2026,35(03):226-231.

ZHAO Jun-yong,WANG Ze-lan,LUO Wen-jian,et al.Role and mechanism of the bromodomain-containing protein 4 inhibitor JQ1 in vascular calcification[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(03):226-231.
赵俊勇,王泽澜,罗稳健等.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[J].局解手术学杂志,2026,35(03):226-231. DOI： 10.11659/jjssx.11E025040.

ZHAO Jun-yong,WANG Ze-lan,LUO Wen-jian,et al.Role and mechanism of the bromodomain-containing protein 4 inhibitor JQ1 in vascular calcification[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(03):226-231. DOI： 10.11659/jjssx.11E025040.

摘要

目的

研究溴结构域蛋白4（BRD4）在血管钙化中的表达情况及其抑制剂JQ1对血管钙化的作用并探讨其潜在的机制。

方法

大鼠血管平滑肌细胞（VSMCs）采用高磷培养诱导钙化，同时添加JQ1处理。采用钙含量测定、Alizarin Red及von Kossa染色评估细胞的钙化情况；使用Western blot检测BRD4、RUNX2以及ACSL4蛋白表达水平。C57BL/6J小鼠采用皮下注射VD

诱导主动脉急性钙化，而后腹腔注射JQ1。采用钙含量测定、Alizarin Red染色评估小鼠主动脉钙化情况；使用Western blot检测BRD4及RUNX2蛋白表达水平。使用NCBI数据库中已发表的ChIP-seq数据分析JQ1对BRD4在ACSL4启动子区域上的富集程度的影响。

结果

钙化VSMCs中BRD4的表达明显上调；JQ1在体内外均明显减轻了血管钙化，下调了BRD4、RUNX2的表达；JQ1明显减少了BRD4在ACSL4启动子区域的富集，抑制了ACSL4的转录活性。

结论

JQ1抑制血管钙化，可能与下调BRD4的表达进而降低了ACSL4的转录活性，最终抑制VSMCs铁死亡有关。

Abstract

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 trea

ted 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 VD

， 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.

关键词

Keywords

references

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