Department of Cell and Molecular Physiology, Loyola University Chicago, 2160 S. 1st Ave, Maywood, IL, 60153, USA.
Curr Cardiol Rep. 2023 Jun;25(6):473-484. doi: 10.1007/s11886-023-01876-9. Epub 2023 Apr 15.
The pace of identifying cardiomyopathy-associated mutations and advances in our understanding of sarcomere function that underlies many cardiomyopathies has been remarkable. Here, we aim to synthesize how these advances have led to the promising new treatments that are being developed to treat cardiomyopathies.
The genomics era has identified and validated many genetic causes of hypertrophic and dilated cardiomyopathies. Recent advances in our mechanistic understanding of sarcomere pathophysiology include high-resolution molecular models of sarcomere components and the identification of the myosin super-relaxed state. The advances in our understanding of sarcomere function have yielded several therapeutic agents that are now in development and clinical use to correct contractile dysfunction-mediated cardiomyopathy. New genes linked to cardiomyopathy include targets with limited clinical evidence and require additional investigation. Large portions of cardiomyopathy with family history remain genetically undiagnosed and may be due to polygenic disease.
鉴定心肌病相关突变的步伐以及对许多心肌病所基于的肌节功能的理解的进步是显著的。在这里，我们旨在综合这些进展如何导致正在开发的治疗心肌病的有前途的新疗法。
基因组学时代已经确定和验证了许多肥厚型和扩张型心肌病的遗传原因。我们对肌节病理生理学的机制理解的最新进展包括肌节成分的高分辨率分子模型和肌球蛋白超级松弛状态的鉴定。对肌节功能的理解的进展产生了几种治疗剂，这些治疗剂现在正在开发和临床应用中，以纠正收缩功能障碍介导的心肌病。与心肌病相关的新基因包括具有有限临床证据的靶点，需要进一步研究。具有家族史的大部分心肌病在遗传上仍未得到诊断，可能是多基因疾病所致。
