-葡萄糖共传输体2抑制剂通过抑制内网膜蛋白质雷多克素域含有5个依赖性骨质性重编程的抑制血管化,从而减弱血管化
Shaofa Wu1, Xiaolin Luo2, Yang Chen2
1Department of Cardiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China; Department of Nephrology, Youyang Hospital, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 409800, China.
Redox biology
|May 17, 2024
概括
-葡萄糖共运输体2 (SGLT2) 抑制剂通过降低TXNDC5的调节来降低血管化,防止Runx2降解. 这些发现表明,SGLT2抑制剂对预防和治疗血管化有前途.
科学领域:
- 心血管医学 心血管医学
- 内分泌学 在内分泌学.
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 血管化显著增加心血管事件的风险,但有效的治疗方法仍然有限.
- 主要用于糖尿病的-葡萄糖共运输体2 (SGLT2) 抑制剂显示出潜在的心血管益处,包括对血管化的影响.
- 通过SGLT2抑制剂影响血管化的精确机制尚未完全理解.
研究的目的:
- 研究SGLT2抑制剂对血管化的保护作用.
- 阐明涉及SGLT2抑制剂介导的血管化预防的潜在分子机制.
主要方法:
- 分析了1554名2型糖尿病患者的冠状动脉CT血管学数据,以将SGLT2抑制剂使用与化评分相关联.
- 使用慢性病和西方饮食诱导的动脉样的动物模型进行体内研究,以评估达帕格利弗洛辛 (DAPA) 对血管化的影响.
- 使用血管光滑肌细胞 (VSMC) 进行体外研究,以检查DAPA对骨质变异,TXNDC5表达,Runx2稳定性和内质网膜 (ER) 压力的影响.
- 转录组分析以确定关键分子参与者,随后进行救援实验以验证发现.
- 在相关的化模型中使用empagliflozin验证类效应.
主要成果:
- 在2型糖尿病患者中,使用SGLT2抑制剂与较低的冠状动脉化得分有关.
- 在多个临床前模型中,达帕格利弗洛辛 (DAPA) 显著降低了亲密和中间血管化.
- 通过降低TXNDC5的调节,DAPA抑制了VSMC的骨质变异,这稳定了Runx2并减少了其蛋白质体降解.
- DAPA改善了ER压力和氧化压力,导致TXNDC5表达的减少.
- 恩帕格利弗洛辛在血管化上表现出类似的类效应.
结论:
- SGLT2 抑制剂通过抑制ER压力诱导的TXNDC5上调和促进Runx2蛋白质体降解,有效地改善血管化.
- 这些发现突出了SGLT2抑制剂在心血管保护中的新机制.
- SGLT2 抑制剂代表了预防和治疗血管化的潜在治疗策略.
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