印度尔-3-酸保护心力衰竭与保存的喷射分数保护
Yu-Chen Wang1, Yen Chin Koay2,3, Calvin Pan1
1Department of Medicine, Division of Cardiology, Department of Microbiology, Immunology and Molecular Genetics, and Department of Human Genetics, University of California, Los Angeles (Y.-C.W., C.P., Z.Z., A.J.L.).
Circulation research
|January 24, 2024
概括
印-3-酸 (IPA) 通过改善腹功能来保护心脏衰竭与保存的喷射分数 (HFpEF). 补充IPA或改变肠道细菌可能为HFpEF提供治疗策略.
科学领域:
- 心脏病学 心脏病学
- 代谢学 代谢学 代谢学
- 微生物组研究 微生物组研究
背景情况:
- 保持喷射分数 (HFpEF) 的心力衰竭是一种复杂的疾病,具有失效的透析功能.
- HFpEF的特点是异质性和多种并发症,如肥胖和糖尿病,使研究复杂化.
- 在HFpEF模型中观察到降低了肠道细菌代谢产物 indole-3-propionic acid (IPA) 的水平.
研究的目的:
- 为了研究英多尔-3-酸 (IPA) 在心力衰竭中所扮演的角色,保留喷射分数 (HFpEF).
- 在HFpEF小鼠模型和人类队伍中评估IPA的治疗潜力.
主要方法:
- 在HFpEF小鼠模型中进行代谢分析,以确定降低的IPA水平.
- 在HFpEF小鼠模型中用IPA补充食.
- 在两个独立的人类HFpEF队列中检查IPA水平.
- 研究了涉及尼古丁胺胺 N-甲基转移酶 (NNMT),尼古丁胺胺氨基二核酸 (NAD+) /NADH 和三素 (SIRT3) 的机制.
主要成果:
- 在HFpEF小鼠中,IPA补充剂减轻了腹功能障碍,炎症,氧化应激和肠道功能障碍.
- 通过抑制NNMT,IPA恢复了心脏中的尼古丁胺,NAD+/NADH和SIRT3水平.
- IPA的保护作用通过基碳化合物受体和SIRT3进行介导,并通过敲击研究得到证实.
- 在人类HFpEF患者中发现IPA水平显著降低.
结论:
- 在HFpEF中,IPA证明了对扩张性功能障碍的保护作用.
- IPA增强了尼古丁胺胺氨基二核酸救援途径.
- 治疗策略可能涉及调节肠道微生物群或IPA食补充剂的HFpEF.
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