Molecular Genetics, Cardiovascular Institute, University of Colorado Denver Anschutz Medical Campus, 12700 E 19th Ave #F442, Aurora, CO, 80045-2507, USA.
Department of Engineering and Architecture, University of Trieste (Italy), Trieste, Italy.
Curr Cardiol Rep. 2019 Nov 26;21(12):160. doi: 10.1007/s11886-019-1224-7.
The purpose of this review is to provide an update on lamin A/C (LMNA)-related cardiomyopathy and discuss the current recommendations and progress in the management of this disease. LMNA-related cardiomyopathy, an inherited autosomal dominant disease, is one of the most common causes of dilated cardiomyopathy and is characterized by steady progression toward heart failure and high risks of arrhythmias and sudden cardiac death.
We discuss recent advances in the understanding of the molecular mechanisms of the disease including altered cell biomechanics, which may represent novel therapeutic targets to advance the current management approach, which relies on standard heart failure recommendations. Future therapeutic approaches include repurposed molecularly directed drugs, siRNA-based gene silencing, and genome editing. LMNA-related cardiomyopathy is the focus of active in vitro and in vivo research, which is expected to generate novel biomarkers and identify new therapeutic targets. LMNA-related cardiomyopathy trials are currently underway.
本文旨在介绍核纤层蛋白 A/C（LMNA）相关性心肌病，并讨论该疾病的治疗推荐和进展。LMNA 相关性心肌病是一种常见的遗传性常染色体显性疾病，是扩张型心肌病的最常见病因之一，其特征为逐渐进展为心力衰竭，心律失常和心源性猝死风险高。
我们讨论了疾病分子机制的最新进展，包括细胞生物力学的改变，这可能代表新的治疗靶点，以推进目前依赖于心力衰竭标准治疗建议的治疗方法。未来的治疗方法包括重新定位的靶向分子药物、基于 siRNA 的基因沉默和基因组编辑。LMNA 相关性心肌病是目前体外和体内研究的重点，预计将产生新的生物标志物并确定新的治疗靶点。目前正在进行 LMNA 相关性心肌病的临床试验。
