由宿主GPR41/43感知的肠道微生物群代谢物可以防止高血压
Rikeish R Muralitharan1, Tenghao Zheng1, Evany Dinakis1
1Hypertension Research Laboratory, Victorian Heart Institute and Department of Pharmacology, Biomedical Discovery Institute, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, Australia (R.R.M., T.Z., E.D., L.X., A.B.-W., H.A.J., M.N., M.P., K.C.L., W.Q., J.A.O.D., F.Z.M.).
Circulation research
|January 22, 2025
概括
缺乏短链脂肪酸受体GPR41和GPR43的信号传递会加剧高血压并恶化心血管结果. 准这些受体可能为预防和治疗高血压提供一种新的策略.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 心血管科学 心血管科学
背景情况:
- 肠道微生物群将食纤维发酵成短链脂肪酸 (SCFA),这些脂肪酸具有心脏保护作用.
- SCFA通过G蛋白结合受体GPR41和GPR43发出信号,主要是在免疫细胞上.
- GPR41和GPR43在高血压中的作用以及纤维的心脏保护作用仍然不清楚.
研究的目的:
- 研究GPR41和GPR43在高血压中的作用以及食纤维的心脏保护作用.
- 为了确定GPR41/43信号是否介导高纤维饮食的心血管益处.
主要方法:
- 在不同的纤维饮食和血管激素II治疗下,在GPR41/43淘汰赛小鼠和野生型小鼠中评估了心血管表型.
- 使用了类似收费受体4 (TLR4) 抗剂治疗和骨髓模拟物.
- 在英国生物库参与者中分析了与GPR41/43表达相关的单核酸多态 (SNP).
主要成果:
- GPR41/43淘汰赛小鼠表现出加剧的高血压,心脏和脏原沉积增加,肠道透性增加.
- 对TLR4抗剂的治疗改善了淘汰小鼠的高血压表型.
- 免疫细胞中缺乏GPR41/43足以使高血压恶化.
- GPR41/43受体部分负责高纤维饮食的降血压和心脏保护作用.
- 高血压与与人类较低GPR41/43表达相关的遗传变异有关.
结论:
- 通过GPR41和GPR43传递SCFA信号的缺失会增加高血压的风险.
- 准GPR41和GPR43为高血压提供了一个潜在的新疗法策略.
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