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Inflammation and Immune Response in Arrhythmogenic Cardiomyopathy: State-of-the-Art Review
Circulation ( IF 37.8 ) Pub Date : 2021-11-15 , DOI: 10.1161/circulationaha.121.055890
Babken Asatryan 1 , Angeliki Asimaki 2 , Andrew P Landstrom 3, 4 , Mohammed Y Khanji 5, 6, 7 , Katja E Odening 1, 8 , Leslie T Cooper 9 , Francis E Marchlinski 10 , Anna R Gelzer 11 , Christopher Semsarian 12, 13 , Tobias Reichlin 1 , Anjali T Owens 14 , C Anwar A Chahal 5, 10, 15, 16
Affiliation  

Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium, predominantly caused by genetic defects in proteins of the cardiac intercalated disc, particularly, desmosomes. Transmission is mostly autosomal dominant with incomplete penetrance. ACM also has wide phenotype variability, ranging from premature ventricular contractions to sudden cardiac death and heart failure. Among other drivers and modulators of phenotype, inflammation in response to viral infection and immune triggers have been postulated to be an aggravator of cardiac myocyte damage and necrosis. This theory is supported by multiple pieces of evidence, including the presence of inflammatory infiltrates in more than two-thirds of ACM hearts, detection of different cardiotropic viruses in sporadic cases of ACM, the fact that patients with ACM often fulfill the histological criteria of active myocarditis, and the abundance of anti–desmoglein-2, antiheart, and anti-intercalated disk autoantibodies in patients with arrhythmogenic right ventricular cardiomyopathy. In keeping with the frequent familial occurrence of ACM, it has been proposed that, in addition to genetic predisposition to progressive myocardial damage, a heritable susceptibility to viral infections and immune reactions may explain familial clustering of ACM. Moreover, considerable in vitro and in vivo evidence implicates activated inflammatory signaling in ACM. Although the role of inflammation/immune response in ACM is not entirely clear, inflammation as a driver of phenotype and a potential target for mechanism-based therapy warrants further research. This review discusses the present evidence supporting the role of inflammatory and immune responses in ACM pathogenesis and proposes opportunities for translational and clinical investigation.

中文翻译:

致心律失常性心肌病的炎症和免疫反应:最先进的综述

致心律失常性心肌病(ACM)是心肌的原发性疾病,主要由心脏间盘蛋白,特别是桥粒的遗传缺陷引起。传播主要是常染色体显性遗传,外显率不完全。ACM 还具有广泛的表型变异性,从室性早搏到心源性猝死和心力衰竭。在表型的其他驱动因素和调节因素中,对病毒感染和免疫触发的炎症反应被认为是心肌细胞损伤和坏死的加重因素。这一理论得到多项证据的支持,包括超过三分之二的 ACM 心脏存在炎症浸润,在散发的 ACM 病例中检测到不同的心脏病毒,ACM 患者通常符合活动性心肌炎的组织学标准,以及致心律失常性右心室心肌病患者存在大量抗桥粒芯糖蛋白-2、抗心脏和抗闰盘自身抗体。为了与 ACM 的频繁家族性发生保持一致,有人提出,除了进行性心肌损伤的遗传易感性之外,对病毒感染和免疫反应的遗传易感性也可以解释 ACM 的家族聚集性。此外,大量体外和体内证据表明 ACM 中激活的炎症信号传导。尽管炎症/免疫反应在 ACM 中的作用尚不完全清楚,但炎症作为表型的驱动因素和基于机制的治疗的潜在靶点值得进一步研究。
更新日期:2021-11-16
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