肠道微生物群-胆酸-TGR5轴协调血小板激活和动脉血症
Zhiyong Qi1, Wei Zhang2, Peng Zhang1
1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, China.
Nature cardiovascular research
|April 11, 2025
概括
降低脱氧胆酸 (DCA) 和冠状动脉疾病 (CAD) 患者的肠道细菌损害了胆酸代谢. DCA通过TGR5抑制了血小板激活,这表明肠道微生物群和胆酸向于CAD血栓症治疗.
科学领域:
- 心血管医学 心血管医学
- 微生物组研究 微生物组研究
- 代谢性疾病研究研究
背景情况:
- 由肠道微生物群产生的胆酸是代谢疾病的关键.
- 胆汁酸在冠状动脉疾病 (CAD) 中的血小板激活和血栓形成中的作用尚不清楚.
- 患有CAD的患者表现出脱氧醇酸 (DCA) 的降低和减少*Bacteroides vulgatus*.
研究的目的:
- 调查肠道微生物群衍生胆酸对血小板激活和CAD中血栓形成的影响.
- 阐明DCA影响血小板功能的机制.
- 探索调节肠道微生物群和CAD相关血栓的胆酸代谢的治疗潜力.
主要方法:
- 在CAD患者中分析血清DCA水平和肠道微生物群组成.
- 使用了Takeda的G蛋白结合受体5 (TGR5) 抑制剂和淘汰赛小鼠模型.
- 在ApoE-/-小鼠中,通过口腔便给药DCA,*B. vulgatus*和健康的便.
主要成果:
- 发现DCA通过与血小板TGR5.5相互作用来抑制激素诱导的血小板激活和血栓形成.
- 口服DCA,B. vulgatus或健康的便抑制了动脉样硬化小鼠的血小板过敏反应和血栓形成.
- 治疗减少了微血管血栓形成,并保护了心脏免受心肌缺血/再输伤害.
结论:
- 脱氧胆酸 (DCA) 在抑制血小板激活和血栓形成方面发挥着重要作用.
- 针对肠道微生物群和胆酸代谢,为CAD相关的血栓形成提供了潜在的治疗策略.
- 调节肠道微生物组和DCA水平可能为心血管疾病提供新的治疗方法.
相关概念视频
01:17Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
01:22Formation of the Platelet Plug
3.4K
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
3.4K
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
436
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
436
01:18Structure and Function of Platelets
929
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
929
01:38Inflammation
52.1K
Overview
52.1K
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
583
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
583