Sirt3 缺乏会促进内皮功能障碍,并加重损伤
Anna Pezzotta1, Luca Perico1, Daniela Corna1
1Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.
PloS one
|October 10, 2023
概括
线粒体Sirtuin 3 (SIRT3) 缺乏会损害脏内皮功能,并加剧毒素损伤. SIRT3对于维持脏血管健康至关重要,并且可能是渐进性脏疾病的治疗点.
科学领域:
- 线粒体生物学 线粒体生物学
- 脏生理学 脏生理学
- 血管生物学 血管生物学
背景情况:
- 赛尔图因3 (SIRT3) 是一种调节新陈代谢和氧化应激的线粒体脱乙酶.
- SIRT3在脏内皮细胞中的作用及其对脏疾病进展的影响尚不清楚.
- 众所周知,状细胞和细胞等高能耗细胞受到SIRT3.3的影响.
研究的目的:
- 研究SIRT3在调节内皮细胞功能中的作用.
- 为了确定SIRT3缺乏对病进展的影响.
- 探索SIRT3作为脏疾病的潜在治疗点.
主要方法:
- 使用全身Sirt3缺乏的小鼠和野生类型的 littermates.
- 用Adriamycin (ADR) 作为毒性刺激剂.
- 评估毛细血管密度,VEGFA表达,缺氧信号 (HIF-1α,安吉奥皮埃丁-2),氧化应激,白蛋白尿,细胞计数和纤维化.
主要成果:
- 缺少Sirt3的小鼠显示毛细血管密度降低,VEGFA信号受损,活性缺氧通路,氧化应激增加.
- 虽然单独缺乏Sirt3并不会导致脏疾病,但接受ADR治疗的缺乏Sirt3的小鼠表现出恶化的内皮稀疏,改变的VEGFA信号和更高的氧化应激.
- 与对照组相比,接受ADR治疗的Sirt3缺乏的小鼠患有更严重的损伤,包括增加的白蛋白尿,细胞损失和纤维性病变.
结论:
- SIRT3对于维持血管平衡和保护损伤至关重要.
- SIRT3失调是导致进展性病的诱导因素.
- SIRT3代表了治疗渐进性病的有前途的药理学标.
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