期刊
HEART FAILURE REVIEWS
卷 27, 期 4, 页码 1373-1385出版社
SPRINGER
DOI: 10.1007/s10741-021-10172-z
关键词
Filamins; Cardiomyopathy; FLNC; Cardiomyocytes
资金
- Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) [2016-I2M1-015]
- National Key Research and Development Project of China [2016YFC1300900, 2019YFA0801500]
- National Natural Science Foundation of China [81900343, 31801068]
Cardiomyopathy is a common disease affecting approximately 1 in 500 adults, with Filamin C playing a critical role in sarcomere stability maintenance and its mutations implicated in the pathogenesis of cardiomyopathy. Truncated and non-truncated FLNC variants are associated with different types of cardiomyopathies. Understanding the molecular mechanisms of FLNC-related cardiomyopathy is crucial in developing new therapies for patients with this condition.
Cardiomyopathy affects approximately 1 in 500 adults and is the leading cause of death. Familial cases are common, and mutations in many genes are involved in cardiomyopathy, especially those in genes encoding cytoskeletal, sarcomere, and nuclear envelope proteins. Filamin C is an actin-binding protein encoded by filamin C (FLNC) gene and participates in sarcomere stability maintenance. FLNC was first demonstrated to be a causal gene of myofibrillar myopathy; recently, it has been found that FLNC mutation plays a critical role in the pathogenesis of cardiomyopathy. In this review, we summarized the physiological roles of filamin C in cardiomyocytes and the genetic evidence for links between FLNC mutations and cardiomyopathies. Truncated FLNC is enriched in dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Non-truncated FLNC is enriched in hypertrophic cardiomyopathy and restrictive cardiomyopathy. Two major pathomechanisms in FLNC-related cardiomyopathy have been described: protein aggregation resulting from non-truncating mutations and haploinsufficiency triggered by filamin C truncation. Therefore, it is important to understand the cellular biology and molecular regulation of FLNC to design new therapies to treat patients with FLNC-related cardiomyopathy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据