Sylvius Nicolas, Tesson Frédérique
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Curr Opin Cardiol. 2006 May;21(3):159-65. doi: 10.1097/01.hco.0000221575.33501.58.
In this review, we will outline the most recent and significant findings on the role of the lamin A/C in cardiac diseases.
Mutations in the lamin A/C gene (LMNA) are associated with numerous diseases involving the heart, skeletal muscles, bones, adipose and nervous tissues. LMNA is one of the most prevalent genes in dilated cardiomyopathy in which it is associated with a high risk of dysrhythmias, sudden death and heart failure. Lamins A and C interact with several proteins reflecting their multiple functions, some of which are likely still unknown. No abnormalities specific to dilated cardiomyopathy are emerging from investigations of striated muscles biopsies or fibroblasts from LMNA mutation carriers. An early diagnosis of the disease is difficult. Both animal and cellular models tend to confirm that lamins A and C play a key role in maintaining the nuclear architecture as well as in regulating transcription.
The cardiac phenotype associated to LMNA mutations is now much clearer, but the molecular mechanisms underlying cellular and tissue specific phenotypes are still puzzling. Systematic mutation screenings and cardioverter-defibrillator implantation have been recommended in patients with cardiac symptoms.
在本综述中，我们将概述有关核纤层蛋白A/C在心脏疾病中作用的最新且重要的研究发现。
核纤层蛋白A/C基因（LMNA）的突变与多种累及心脏、骨骼肌、骨骼、脂肪和神经组织的疾病相关。LMNA是扩张型心肌病中最常见的基因之一，在该疾病中它与心律失常、猝死和心力衰竭的高风险相关。核纤层蛋白A和C与多种蛋白质相互作用，反映了它们的多种功能，其中一些功能可能仍不为人知。对LMNA突变携带者的横纹肌活检或成纤维细胞进行研究，未发现扩张型心肌病特有的异常情况。该疾病的早期诊断很困难。动物模型和细胞模型均倾向于证实核纤层蛋白A和C在维持核结构以及调节转录方面起关键作用。
与LMNA突变相关的心脏表型现在已更加清晰，但细胞和组织特异性表型背后的分子机制仍然令人困惑。对于有心脏症状的患者，建议进行系统的突变筛查和植入心脏复律除颤器。
