选择性阻断interleukin 6的传递信号抑制了心房动
Xintao Li1, Xiaoyu Wu2, Xiaoqiang Chen2
1Department of Cardiology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
Heart rhythm
|August 26, 2023
概括
互乐金6 (IL-6) 转信号有助于心房 (AF) 的发展. 用sgp130Fc阻断这种途径减少了小鼠的AF诱导性和心房重塑,这表明了一个新的治疗点.
科学领域:
- 心脏病学 心脏病学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 心房动 (AF) 被认为是一种炎症性心房肌病.
- 干白素6 (IL-6) 信号通路具有上下文依赖的心血管效应,IL-6 跨信号通常是促炎的.
- 对于IL-6跨信号在AF病原体中的特定作用尚不清楚.
研究的目的:
- 研究IL-6转信号在心房的发展中的作用.
- 为了确定阻断IL-6跨信号是否可以减轻AF相关的心房变化.
主要方法:
- 在AF患者和对照群中测量IL-6跨信号标记物 (IL-6,可溶性IL-6受体, sgp130).
- 利用一种由横向大动脉收缩引起的AF的小鼠模型.
- 用SGP130Fc选择性地阻断IL-6转信号,并评估其对AF诱导性,心房导电和结构重塑的影响.
主要成果:
- 升高的IL-6跨信号水平与患者的AF发生呈正相关.
- 在小鼠中,通过SGP130Fc阻断IL-6的转信号,降低了AF的诱导性.
- 施用Sgp130Fc改善了心房导电,减少了纤维化和扩张,使连素表达正常化,降低了免疫细胞透,降低了小鼠心房中的氧化应激.
结论:
- IL-6的跨信号激活是AF发展的一个因素.
- 选择性阻断IL-6转信号呈现出一种潜在的新型治疗策略,用于管理AF.
相关概念视频
The JAK-STAT Signaling Pathway
9.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.0K
Intracellular Signaling Affects Focal Adhesions
2.7K
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...
2.7K
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
463
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
463
Antihypertensive Drugs: Angiotensin II Receptor Blockers
778
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
778
Depolarizing Blockers: Mechanism of Action
1.6K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
1.6K
Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
887
α-Adrenergic antagonists, known as α-blockers, exert their effects by inhibiting α-adrenoceptors, leading to specific physiological actions. α1-blockers and α2-blockers have distinct pharmacological actions and therapeutic applications.
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...
887


