乳酸激活的GPR132-Src信号诱导巨细胞衰老和加剧动脉样硬化 在糖尿病下
Xiaofeng Ge1, Shuying Wang2, Zhaokai Li1
1Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Fujian Branch of National Clinical Research Center for Cardiovascular Diseases, Xiamen University, Xiamen, 361016, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|June 10, 2025
概括
糖尿病通过增加葡萄糖水平促进巨细胞衰老,加速动脉样硬化. 这涉及乳酸,GPR132激活和Src酸化,突出显示了巨细胞衰老作为治疗点.
科学领域:
- 生物医学科学 生物医学科学
- 心血管研究研究心血管研究
- 代谢性疾病研究研究
背景情况:
- 糖尿病是动脉样硬化的主要危险因素.
- 细胞衰老,糖尿病和动脉样硬化与衰老有共同的联系,但它们的相互作用尚不清楚.
- 了解糖尿病和动脉样硬化的联系机制对于开发向疗法至关重要.
研究的目的:
- 为了研究细胞衰老在糖尿病加速动脉样硬化中的作用.
- 为了阐明参与这个过程的特定分子路径.
- 为了确定糖尿病动脉样硬化的潜在治疗点.
主要方法:
- 在体外研究了高葡萄糖对巨细胞衰老和脂质吸收的影响.
- 使用了GPR132删除的小鼠模型,并用萨拉卡提尼布 (Src抑制剂) 治疗.
- 分析了临床样本,以评估血乳酸,GPR132-Src通路激活和冠状动脉狭窄之间的相关性.
主要成果:
- 高血糖诱导巨细胞衰老,增强氧化低密度脂蛋白 (ox-LDL) 的吸收和泡细胞的形成.
- 通过糖解激活GPR132,促进巨细胞衰老和通过Src酸化吸收脂质.
- 在小鼠中,GPR132的删除减少了衰老和动脉样硬化;萨拉卡提尼布缓解了糖尿病动脉样硬化.
- 临床样本显示了血乳酸,PBMC中的GPR132-Src通路激活和冠状动脉狭窄之间的积极关联.
结论:
- 糖尿病通过乳酸-GPR132-Src通路加速动脉样硬化,由巨细胞衰老介导.
- 巨细胞衰老是糖尿病动脉样硬化的发病的一个关键因素.
- 向乳酸-GPR132-Src通路为糖尿病动脉样硬化提供了一个有希望的治疗策略.
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