Pradeep Roshini, Akram Aqsa, Proute Matthew C, Kothur Nageshwar R, Georgiou Petros, Serhiyenia Tatsiana, Shi Wangpan, Kerolos Mina E, Mostafa Jihan A
Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.
Cureus. 2021 Aug 29;13(8):e17548. doi: 10.7759/cureus.17548. eCollection 2021 Aug.
Hypertrophic cardiomyopathy (HCM) is a genetically acquired disease of cardiac myocytes. Studies show that 70% of this disease is a result of different mutations in various sarcomere genes. This review aims to discuss several genetic mutations, epigenetic factors, and signal transduction pathways leading to the development of HCM. In addition, this article elaborates on recent advances in gene therapies and their implications for managing this condition. We start by discussing the founding mutations in HCM and their effect on power stroke generation. The less explored field of epigenetics including methylation, acetylation, and the role of different micro RNAs in the development of cardiac muscle hypertrophy has been highlighted in this article. The signal transduction pathways that lead to gene transcription, which in turn lead to increased protein synthesis of cardiac muscle fibers are elaborated. Finally, the microscopic events leading to the pathophysiologic macro events of cardiac failure, and the current experimental trials of gene therapy models, and the clustered regularly interspaced short palindromic repeats (CRISPR) type 2 system proteins, are discussed. We have concluded our discussion by emphasizing the need for more studies on epigenomics and experimental designs for gene therapy in HCM patients. This review focuses on the process of HCM from initial mutation to the development of phenotypic expression and various points of intervention in cardiac myocardial hypertrophy development.
肥厚型心肌病(HCM)是一种遗传性心肌细胞疾病。研究表明,该疾病70%是由各种肌节基因的不同突变所致。本综述旨在探讨导致HCM发生的几种基因突变、表观遗传因素及信号转导途径。此外,本文还阐述了基因治疗的最新进展及其对该病治疗的意义。我们首先讨论HCM的起始突变及其对动力冲程产生的影响。本文重点介绍了表观遗传学中较少被探索的领域,包括甲基化、乙酰化以及不同微小RNA在心肌肥大发展中的作用。阐述了导致基因转录进而导致心肌纤维蛋白合成增加的信号转导途径。最后,讨论了导致心力衰竭病理生理宏观事件的微观过程、当前基因治疗模型的实验性试验以及2型成簇规律间隔短回文重复序列(CRISPR)系统蛋白。我们在讨论结尾强调,需要对HCM患者的表观基因组学进行更多研究,并开展基因治疗的实验设计。本综述聚焦于HCM从初始突变到表型表达发展的过程以及心肌肥大发展过程中的各个干预点。