心肌细胞受限制的IL11表达导致心脏纤维化,炎症和功能障碍
Mark Sweeney1,2,3, Katie O'Fee1,2, Chelsie Villanueva-Hayes1,2
11MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London W12 0NN, UK.
International journal of molecular sciences
|August 26, 2023
概括
由心脏细胞分泌的互白素11 (IL11) 驱动心脏纤维化和炎症,与之前的发现相反. 这项研究揭示了IL11是心脏病进展的关键因素.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 纤维化研究 纤维化研究
背景情况:
- 心脏纤维化是心脏病的标志和治疗目标.
- 介质蛋白11 (IL11) 具有相互矛盾的作用,一些研究表明它具有心脏保护作用,而另一些研究则通过转化生长因子β (TGFβ) 将其与纤维化有关.
研究的目的:
- 为了研究心肌细胞衍生型介质素11 (IL11) 对心脏病理生物学和活体功能的特定影响.
- 质疑之前关于IL11的心脏保护潜力的报道.
主要方法:
- 通过使用Cre-loxP系统,生成了一种受托莫西芬诱导的小鼠模型,其心肌细胞受限的小鼠表达*Il11*.
- 分析了心脏纤维化,炎症和功能,使用蛋白质检测,大量RNA测序和体内成像.
- 研究了IL11对内皮细胞转移到介质酶细胞的影响.
主要成果:
- 转化生长因子β (TGFβ) 刺激心肌细胞上调调节*Il11*表达.
- 具有心肌细胞特异性IL11表达的心脏表现出严重的心脏纤维化和炎症.
- 升高的IL11水平与增加的细胞因子,化学因子,补充因子,炎症细胞和内皮细胞转移到介质细胞相关,导致左心室功能障碍.
结论:
- 由心肌细胞分泌的与物种相匹配的IL11是心脏中强有力的益纤维和促炎因素.
- 这些发现确立了IL11是心脏病病理学的重要贡献者,挑战了它以前建议的心脏保护作用.
相关概念视频
01:21Myocarditis I: Introduction
9
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...
9
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
16
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...
16
01:30Cardiomyopathy II: Dilated Cardiomyopathy
11
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
11
01:23Rheumatic Heart Disease I: Introduction
16
Rheumatic heart disease or RHD is a chronic condition that results from rheumatic fever, causing permanent damage to the heart valves.Etiology and Risk FactorsIt primarily arises from rheumatic fever, an inflammatory disease that can develop after untreated or inadequately treated group A streptococcal (GAS) pharyngitis. Streptococcus spreads through direct contact with oral or respiratory secretions. While the bacteria are the causative agents, factors like malnutrition, overcrowding, poor...
16
01:29Cardiomyopathy IV: Restrictive Cardiomyopathy
12
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...
12
01:25Cardiomyopathy I: Introduction and Classification
15
Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
15