通过4-PBA抑制内质网膜应激,通过上调CLOCK表达来增强动脉样硬化斑块的稳定性
Guanglang Zhu1, Hongxia Gao1, Yang Li2
1Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Pathology, research and practice
|November 29, 2023
概括
4-甲酸 (4-PBA) 通过减少内分泌网膜 (ER) 应力和增加CLOCK蛋白来改善动脉样硬化斑块的稳定性. 这表明针对ER压力和CLOCK是动脉样硬化的有希望的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞应激反应的应激反应
- 分子医学是分子医学.
背景情况:
- 由未折叠的蛋白质积累引起的内质网膜 (ER) 应激会加剧炎症和疾病.
- 在动脉样硬化斑块的稳定性中ER应激的参与尚未得到充分理解.
- 动脉样硬化包括斑块不稳定,炎症和氧化应激.
研究的目的:
- 调查ER压力抑制剂4-phenylbutyric acid (4-PBA) 对小鼠动脉样硬化斑块稳定性的影响.
- 探索CLOCK蛋白在4-PBA对动脉样硬化的保护作用中的作用.
- 阐明4-PBA调节ER应激和动脉样硬化的细胞过程的机制.
主要方法:
- 吃高脂肪饮食的小鼠接受了4-PBA治疗,以评估斑块的稳定性.
- 在体外研究中使用了氧化低密度脂蛋白 (ox-LDL) 诱导的血管光滑肌细胞 (VSMC).
- 使用短毛RNA (sh-CLOCK) 操纵CLOCK表达,以确定其对4-PBA效应的必要性.
主要成果:
- 在小鼠中,4-PBA治疗显著提高了动脉样硬化斑块的稳定性.
- 4-PBA减少了氧化应激,ER应激标志物 (GRP78,CHOP) 和斑块和VSMC中的亡.
- 4-PBA增加了CLOCK蛋白和mRNA的表达,这对其保护作用至关重要.
结论:
- 用4-PBA抑制ER压力通过上调CLOCK来稳定动脉样硬化斑块.
- 调节CLOCK表达对于4-PBA在动脉样硬化中的治疗益处至关重要.
- 准ER压力和CLOCK代表了治疗动脉样硬化的潜在策略.
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