Scholarlink

Abstract <p>Atherosclerosis (AS) is a fundamental pathological process underlying cardiovascular disease (CVD), which begins with dysfunction in the endothelial system resulting from damage to vascular endothelial cells. Our research demonstrates that the deubiquitinating enzyme USP5 is upregulated in endothelial cells of AS plaques. In vitro, USP5 knockdown enhanced cell viability, whereas attenuated ox-LDL-induced apoptosis, oxidative stress, inflammation, and endothelial dysfunction in HUVECs. In vivo studies in a mouse model of atherosclerosis showed that USP5 inhibition significantly reduced plaque formation, collagen deposition, and inflammatory cell infiltration. Protein mass spectrometry analysis and immunoprecipitation assays show that USP5 interacts with programmed cell death 4 (PDCD4). PDCD4 overexpression rescues USP5 knockdown effects on HUVECs exposed to ox-LDL. This study elucidates the biological functions of the USP5/PDCD4 axis in the injury of cells of the vascular endothelium during AS and suggests that targeting this axis could offer a potential therapeutic strategy for atherosclerosis.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Inhibition of USP5 Attenuates Atherosclerosis by Suppressing PDCD4-Mediated Endothelial Dysfunction: Evidence from In Vitro HUVEC and In Vivo Models

  • 期刊论文

  • 发表日期：

    2025年6月26日

查看全文
  • Yali Chen,
  • Yihuan Wang,
  • Tingting Wu,
  • Xiaolei Guo,
  • Xueyang Bai,
  • Lirui Wang,
  • Peipei Yan,
  • Zhe Zheng,
  • Lili Xiao,
  • Ling Li

摘要

Abstract

Atherosclerosis (AS) is a fundamental pathological process underlying cardiovascular disease (CVD), which begins with dysfunction in the endothelial system resulting from damage to vascular endothelial cells. Our research demonstrates that the deubiquitinating enzyme USP5 is upregulated in endothelial cells of AS plaques. In vitro, USP5 knockdown enhanced cell viability, whereas attenuated ox-LDL-induced apoptosis, oxidative stress, inflammation, and endothelial dysfunction in HUVECs. In vivo studies in a mouse model of atherosclerosis showed that USP5 inhibition significantly reduced plaque formation, collagen deposition, and inflammatory cell infiltration. Protein mass spectrometry analysis and immunoprecipitation assays show that USP5 interacts with programmed cell death 4 (PDCD4). PDCD4 overexpression rescues USP5 knockdown effects on HUVECs exposed to ox-LDL. This study elucidates the biological functions of the USP5/PDCD4 axis in the injury of cells of the vascular endothelium during AS and suggests that targeting this axis could offer a potential therapeutic strategy for atherosclerosis.

Graphical Abstract