SRC抑制通过激活FUNDC1-依赖的线粒细胞衰变来减轻血管衰老.
Linghuan Wang1, Yan Ma2, Tianhu Wang2
1Department of Medicine School, Nankai University, 300071 Tianjin, China; Institute of Geriatric Medicine, National Clinical Research Centre for Geriatric Diseases, National Key Lab for Chronic Kidney Disease, Second Medical Centre of Chinese PLA General Hospital, 100853 Beijing, China.
SRC是一种应激响应的氨酸激酶,调节细胞和血管衰老. 抑制SRC可能通过改善线粒体功能来提供对血管衰老和动脉样硬化的治疗益处.
科学领域:
- 血管生物学 血管生物学
- 细胞衰老 细胞衰老
- 线粒体动力学的动力学
背景情况:
- 血管光滑肌肉细胞衰老驱动血管重塑和动脉样硬化.
- 线粒体功能障碍和线粒体衰竭是血管衰老的关键因素.
- 在血管衰老中SRC (一种应激响应的氨酸激酶) 的作用尚不清楚.
研究的目的:
- 研究SRC在调节血管衰老中的自和髓中所扮演的角色.
- 在血管衰老的背景下探索SRC-FUNDC1轴.
- 评估SRC抑制作为血管衰老和动脉样硬化的潜在治疗策略.
主要方法:
- 在ApoE-/-小鼠中建立了加速血管衰老模型,并在小鼠大动脉血管光滑肌细胞 (MOVAS) 中诱导衰老.
- 使用药理学SRC抑制 (KX2-391) 和基因操纵 (SRC淘汰/过度表达).
- 评估了线粒体流动,线粒体形态,衰老标志物和动脉样硬化斑块特征.
主要成果:
- 在体外和体内血管衰老模型中观察到SRC表达和活性升高.
- SRC抑制部分逆转了血管衰老特征,改善了线粒体形态,并减少了动脉样硬化负担.
- SRC通过FUNDC1 (在Tyr18) 的酸化来调节线粒细胞衰变,这种轴对SRC介导的抗衰老保护至关重要.
结论:
- SRC-FUNDC1轴是线粒和血管衰老的关键调节器.
- 抑制SRC显示出缓解血管衰老和动脉样硬化的治疗潜力.
- 准SRC为治疗与年龄相关的血管疾病提供了一个有希望的途径.
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