A change of heart: new roles for cilia in cardiac development and disease.
A change of heart: new roles for cilia in cardiac development and disease.
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DOI：
10.1038/s41569-021-00635-z
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发表时间：
2022-04
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虽然心脏异常已被观察到在一类日益增长的人类疾病引起的缺陷初级纤毛，纤毛在心脏中的功能仍然是一个未充分探索的领域。长期以来，人们认为心脏中纤毛的主要功能仅限于胚胎发生期间的左右轴模式。然而，新的发现揭示了纤毛在先天性心脏病、瓣膜形成、心肌纤维化和再生以及机械感觉中的广泛作用。在这篇综述中，我们描述了我们对纤毛功能促进心脏左右轴发育的机制的理解，并讨论了最新的发现，这些发现突出了纤毛在心脏发育中的更广泛作用。具体来说，我们研究了越来越多的证据连接纤毛功能的先天性心脏病的发病机制。此外，我们还强调了过去10年的研究，证明了纤毛功能在常见心脏瓣膜疾病中的作用，包括二尖瓣脱垂和主动脉瓣疾病，并描述了可能将血液动力学和收缩力与心脏发育和功能的遗传调节联系起来的机械感觉中涉及心脏纤毛的发现。最后，鉴于心脏成纤维细胞上存在纤毛，我们还探讨了纤毛在纤维化生长中的潜在作用，并总结了心脏纤毛在心脏再生中的证据。
Although cardiac abnormalities have been observed in a growing class of human disorders caused by defective primary cilia, the function of cilia in the heart remains an underexplored area. The primary function of cilia in the heart was long thought to be restricted to left–right axis patterning during embryogenesis. However, new findings have revealed broad roles for cilia in congenital heart disease, valvulogenesis, myocardial fibrosis and regeneration, and mechanosensation. In this Review, we describe advances in our understanding of the mechanisms by which cilia function contributes to cardiac left–right axis development and discuss the latest findings that highlight a broader role for cilia in cardiac development. Specifically, we examine the growing line of evidence connecting cilia function to the pathogenesis of congenital heart disease. Furthermore, we also highlight research from the past 10 years demonstrating the role of cilia function in common cardiac valve disorders, including mitral valve prolapse and aortic valve disease, and describe findings that implicate cardiac cilia in mechanosensation potentially linking haemodynamic and contractile forces with genetic regulation of cardiac development and function. Finally, given the presence of cilia on cardiac fibroblasts, we also explore the potential role of cilia in fibrotic growth and summarize the evidence implicating cardiac cilia in heart regeneration.
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