准S100A9可以防止β-上腺激活诱导的心脏损伤
Jie Liu1, Xin Chen1, Lijun Zeng1
1Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Army Medical University, Chongqing, 400038, People's Republic of China.
Inflammation
|March 6, 2024
概括
针对S100A9,这是损伤相关分子模式 (DAMPs) 的关键组成部分,可以防止心力衰竭的进展. 这种方法减少了心脏炎症和纤维细胞-巨细胞相互作用,为心脏纤维化治疗提供了双重好处.
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:
- 改变的心脏天生的免疫力有助于心力衰竭的进展.
- S100A8/A9,一种与损伤相关的分子模式 (DAMP),与心力衰竭的发病有关.
- S100A8/A9是心力衰竭的潜在治疗点.
研究的目的:
- 为了验证S100A8/A9在心脏损伤和心力衰竭中的作用.
- 评估帕基尼莫德作为S100A8 / A9激活的药理干预措施.
- 阐明S100A8/A9在促进心脏纤维化的机制.
主要方法:
- 验证S100A8/A9在心力衰竭的β-上腺素过活化模型中的作用.
- 用帕基尼莫德治疗,以评估其治疗潜力.
- 使用腺相关病毒 (AAV) 9介导的短毛RNA (shRNA) 进行心肌细胞特异性的S100A9沉默.
- 研究心脏纤维化中的纤维细胞-巨细胞相互作用.
主要成果:
- 激活S100A8/A9有助于心脏功能障碍,原沉积,炎症和免疫细胞透.
- 帕基尼莫德治疗改善了心脏功能障碍和纤维化.
- S100A9沉默证实了它在心脏病理学中的作用.
- 激活的S100A8/A9促进纤维细胞-巨细胞相互作用,独立于炎症,增强原蛋白的产生.
结论:
- 针对S100A9提供了通过抵消心脏炎症和防止心脏纤维细胞-巨细胞相互作用的双重好处.
- 抑制S100A9是一种治疗心脏纤维化和心力衰竭的有希望的策略.
- 这些发现支持S100A9作为未来心血管疾病药物开发的潜在目标.
相关概念视频
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
429
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...
429
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
801
β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in...
801
01:22Heart Failure Drugs: β-Blockers
338
β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
338
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
447
Third-generation β-blockers, such as labetalol and carvedilol, represent a significant advancement in managing cardiovascular conditions. Unlike conventional β-blockers, which can induce peripheral vasoconstriction, third-generation drugs block α1 adrenoceptors. This promotes vasodilation through several mechanisms, such as increased nitric oxide production, inhibition of calcium ion entry, opening of potassium ion channels, and antioxidant action. Labetalol, for instance, is...
447
01:26Heart Failure Drugs: Inotropic Agents
586
Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
586
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K