甲基康尼丁:在心力衰竭中增强心脏功能的有希望的ACE2向激动剂
Qi-Qiang Zhang1, Qing-Shan Chen1, Fei Feng2
1Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Free radical biology & medicine
|February 18, 2024
概括
班佐伊拉克尼因通过向血管酶转化酶2 (ACE2) 来改善心力衰竭. 这种天然产品通过抑制线粒体反应性氧物种和通过ACE2激活NF-κB来减少心脏缩和纤维化.
科学领域:
- 心血管研究研究心血管研究
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 黄是一种用于心血管疾病的天然产品.
- 其精确的药理效应,直接的蛋白质点,以及心力衰竭治疗中的分子机制在很大程度上是未知的.
研究的目的:
- 阐明佐伊拉克尼在治疗心力衰竭中的直接标蛋白和分子机制.
- 为了研究本佐伊拉康尼丁作为ACE2激动剂的治疗潜力.
主要方法:
- 有限蛋白质解质质谱法 (LiP-MS) 用于识别直接的蛋白质标.
- 在实验室中使用大鼠初级心肌细胞和纤维细胞的研究.
- 在体内研究使用横向大动脉收缩 (TAC) 鼠标模型.
- 在ACE2-敲除细胞和ACE2-敲除 (ACE2-/-) 鼠标模型中.
- 对RNA测序的分析.
主要成果:
- 甲基康尼丁抑制了Ang II诱导的心肌细胞缩和纤维化,并在TAC小鼠中减轻了心脏功能障碍和重塑.
- 鉴定出ACE2是佐伊拉康尼丁的直接结合标.
- 在ACE2-敲击细胞和ACE2-/-小鼠中,本佐伊拉克尼的治疗作用被废除了.
- 本佐伊拉克尼因通过ACE2.2抑制了p38/ERK介导的线粒体ROS和NF-κB通路的激活.
结论:
- 班佐伊拉克尼因作为治疗心力衰竭的有前途的ACE2激动剂.
- 它通过通过ACE2调节线粒体ROS释放和炎症来改善心脏功能.
- 准ACE2的佐伊拉克诺尼丁为心力衰竭提供了一种新的治疗策略.
相关概念视频
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
431
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...
431
01:22Heart Failure Drugs: β-Blockers
340
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,...
340
01:26Heart Failure Drugs: Inotropic Agents
588
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...
588
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
513
Angina pectoris, a primary symptom of ischemic heart disease, requires careful pharmacological interventions. In this context, calcium channel blockers (CCBs) and ranolazine have emerged as crucial pharmacotherapeutic agents, providing deep insights into the complexities of angina management.
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
513
01:22Heart Failure Drugs: Diuretics
381
Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
381
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
638
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
638