异黄胺修饰心脏蛋白驱动心脏中的CD4+T细胞激活并促进心脏功能障碍
在PubMed上查看摘要
概括
此摘要是机器生成的。在心力衰竭中,氧化应激会产生激活T细胞的蛋白质,从而导致心脏功能障碍. 阻断这些isolevuglandin (IsoLG) 修饰会阻止T细胞受体 (TCR) 的激活,并保护心脏.
科学领域
- 心脏病学
- 免疫学
- 生物化学
背景情况
- 由T细胞引起的炎症与非缺血性心力衰竭有关.
- 心脏衰竭进展中的T细胞激活和参与抗原的机制尚不清楚.
研究的目的
- 调查心肌氧化应激是否会产生以isolevuglandin (IsoLG) 修饰的蛋白质作为心脏新抗原.
- 确定这些新抗原是否引起CD4+T细胞受体 (TCR) 激活并促进心力衰竭.
主要方法
- 使用过横动脉收缩的小鼠模型来诱导氧化应激和T细胞透.
- 使用MHCII类缺陷小鼠分析TCR谱,评估抗原呈现,并使用TCR转基因小鼠.
- 在人类心脏衰竭中检测到IsoLG adducts,并评估了抗氧化剂和IsoLG清除剂在体内和体外的作用.
主要成果
- 在心脏功能障碍期间,TCR抗原识别和特定的CD4+T细胞克隆类型在左心室增加.
- 抗原呈现对心脏功能障碍至关重要;MHCII类缺陷和OTII类缺陷的小鼠得到了保护.
- 使用IsoLG可降低TCR激活,防止心脏功能障碍;使用IsoLG修饰的蛋白质可诱导CD4+T细胞的增殖.
结论
- 活性氧物种诱导的IsoLG修饰心脏新抗原驱动心脏中TCR依赖的CD4+T细胞激活.
- 这种途径在心力衰竭的发病过程中起着重要作用.
相关概念视频
Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
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...
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...

