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与心血管疾病相关的肠道微生物代谢物通过上腺体受体起作用
Ina Nemet1, Prasenjit Prasad Saha1, Nilaksh Gupta1
1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Center for Microbiome & Human Health, Cleveland Clinic, Cleveland, OH 44106, USA.
Cell
|March 7, 2020
概括
一种新发现的肠道微生物代谢物,甲胺 (PAGln),通过增强血小板激活和血栓形成,促进心血管疾病 (CVD). 这种代谢物通过上腺体受体发出信号,为预防心血管疾病提供了潜在的新点.
科学领域:
- 微生物学
- 代谢学
- 心血管科学
背景情况:
- 肠道微生物代谢物在宿主健康和疾病中起作用.
- 乙胺 (PAGln) 是一种与心血管疾病 (CVD) 相关的代谢物.
研究的目的:
- 研究PAGln在心血管疾病和血栓形成中的作用.
- 阐明涉及PAGln生产和功能的微生物通路和宿主信号机制.
主要方法:
- 在大型人群中 (n=1,162和n=4,000) 的非向代谢.
- 用全血和分离的血小板进行体外研究.
- 使用动脉损伤和无细菌小鼠的动物模型进行体内研究.
- 人类开始生长的细菌的功能和基因工程.
- 用遗传学和药理学工具进行功能增加和丧失的研究.
主要成果:
- 血PAGln水平与心血管疾病和主要不良事件有关.
- 微生物的 porA 基因促进了氨酸转化为酸,从而产生PAGln.
- 增强血小板激活和血栓形成的可能性.
- PAGln通过上腺体受体 (α2A,α2B,β2) 调解其作用.
结论:
- PAGln是一种新型肠道微生物群依赖的代谢物,促进心血管疾病.
- PAGln通过上腺体受体作用,增加血小板反应和血栓形成.
- 针对PAGln或其信号通路可能为心血管疾病提供新的治疗策略.
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