盐诱导的肝炎记忆通过SIRT3的表观基因调节导致心血管损伤
1Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Chongqing Institute of Hypertension (P.G., M.Y., L.L., X.W., Q. Zhou, H.Z., Z.L., L.W., F.S., D.L., Z.Y., Z.Z.), Army Medical University, Chongqing China.
Circulation
|January 31, 2022
概括
高盐摄入会导致肝脏损伤和心血管问题, 通过像甲素这样的干预措施恢复三蛋白3 (SIRT3) 表达,可以逆转这些有害影响.
科学领域:
- 心血管疾病研究
- 肝病学
- 表观遗传学
背景情况:
- 高盐摄入量是心血管疾病的主要危险因素.
- 非酒精性脂肪肝 (NAFLD) 与高盐摄入有关,是独立的心血管疾病风险因素.
- 盐引起的肝损伤与心血管疾病发展之间的直接联系尚不清楚.
研究的目的:
- 调查盐引起的肝损伤是否有助于心血管疾病的发展.
- 在高盐条件下阐明导致持续性肝炎和心血管疾病的分子机制.
- 评估甲胺在减轻盐引起的损伤方面的治疗潜力.
主要方法:
- 给小鼠提供高盐或正常饮食8周.
- 对高盐养的小鼠进行了脱盐和甲胺治疗.
- 使用基因表达,淘汰模式 (SIRT3,NRF2,AMPK) 和表观遗传分析 (H3K27ac).
主要成果:
- 在小鼠中,高盐饮食诱导肝硬化,炎症,高血压和心脏功能障碍.
- 这些病理变化显示,在戒盐后,持续存在"记忆现象".
- 由于基因组修饰 (H3K27ac) 抑制NRF2结合,导致的Sirtuin 3 (SIRT3) 表达的减少被确定为持续性炎症和心血管疾病的原因.
- 甲胺激活AMPK,减少H3K27ac,恢复NRF2结合,增加SIRT3表达,并逆转肝炎和心血管疾病.
结论:
- 在高盐摄入的情况下,通过组织蛋白修饰抑制SIRT3对持续性肝损伤和心血管疾病至关重要.
- 针对表观遗传修饰的干预措施,以及盐的限制,可以预防持续的炎症和心血管疾病.
- 维持足够的SIRT3表达对于减轻高盐诱导的心血管风险至关重要.
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