Journal article

Paracrine signalling by cardiac calcitonin controls atrial fibrogenesis and arrhythmia

Lucia M Moreira, Abhijit Takawale, Mohit Hulsurkar, David A Menassa, Agne Antanaviciute, Satadru K Lahiri, Neelam Mehta, Neil Evans, Constantinos Psarros, Paul Robinson, Alexander J Sparrow, Marc-Antoine Gillis, Neil Ashley, Patrice Naud, Javier Barallobre-Barreiro, Konstantinos Theofilatos, Angela Lee, Mary Norris, Michele V Clarke, Patricia K Russell Show all

Nature | NATURE RESEARCH | Published : 2020

Abstract

Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans1. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies2. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism3, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and..

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Grants

Awarded by Wellcome Trust


Awarded by Oxford BHF Centre of Research Excellence (CRE)


Awarded by BHF



Funding Acknowledgements

We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the ACF microarrays data; M. Farrall for the help with statistics; K. Clark in the WIMM Flow Cytometry Facility for his help; J. Digby for assistance with analysis and detection of CT by ELISA in human ACFs and ACMs; C. St-Cyr for managing, handling and genotyping mouse colonies at the Montreal site; R. Hiram for initial help with EP analysis in mice; J. Dewing for creating an artistic sketch summary of the main findings; L. E. Schmidt and X. Yin for help with the proteomic experiments; S. Farid and V. Srivastava for help with collection of some human atrial specimens during revision; P. Wookey for advice on CTR protein detection; R. Wijesurendra and P. Gajendragadkar for initial help in obtaining patient consent for the study; and A. Recalde and M. C. Carena for initial help with optimizing the fibroblast isolation protocol. Funded by the British Heart Foundation (BHF) Intermediate Fellowship in Basic Science, the Oxford BHF Centre of Research Excellence (CRE; RG/13/1/30181) Transitional Fellowship, a BHF CRE Overseas Collaboration Travel award, the Medical Science Division Internal Fund, the Wellcome Trust Institutional Strategic Support Fund, the Oxfordshire Health Services Research Committee, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and LAB282 grants (to S.R.); BHF Chair award CH/16/1/32013 (to K.M.C.); the Canadian Institutes of Health Research (CIHR) and Heart and Stroke Foundation of Canada (to S.N.); and Fonds de Recherche en Sante de Quebec (FRQS) and CIHR postdoctoral fellowships to A.T.