A change of heart: new roles for cilia in cardiac development and disease

• Published in: Nature reviews cardiology 2022-04, Vol.19 (4), p.211-227
• Main Authors: Djenoune, Lydia, Berg, Kathryn, Brueckner, Martina, Yuan, Shiaulou
• Format: Article
• Language: English
• Subjects: 631/136/2060; 692/4019/592/2725; 692/4019/592/2726; 692/4019/592/2727; Cardiac Imaging; Cardiac Surgery; Cardiology; Cardiomyopathies - pathology; Cardiovascular disease; Cilia - genetics; Cilia - pathology; Congenital diseases; Fibrosis; Heart; Heart Defects, Congenital - pathology; Heart Valve Diseases; Hemodynamics; Humans; Medicine; Medicine & Public Health; Review Article; Roles
• ISSN: 1759-5002; 1759-5010
• DOI: 10.1038/s41569-021-00635-z

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. Cilia are now known to have broad roles in cardiac development and disease. In this Review, Yuan and colleagues discuss the latest findings that link cilia function and biogenesis to congenital heart disease and describe the role of cilia in the development of cardiac left–right asymmetry, haemodynamic mechanosensation, valvulogenesis and myocardial regeneration. Key points Cilia are antenna-like organelles that extend from most eukaryotic cells to obtain and interpret information from the extracellular environment; impaired ciliary signalling has been linked with congenital heart disease. Intraciliary calcium signalling in the embryonic left–right organizer initiates vertebrate left–right patterning; abnormal left–right asymmetry is associated with major congenital heart disease, especially in heterotaxy syndrome. Impaired cilia function and signalling are associated with heterotaxy, congenital heart disease, mitral valve prolapse and numerous other cilia-related disorders with cardiac abnormalities. Primary cilia have a role in heart develo