Imperial College London
Alternate

DrAlexanderLyon

Faculty of Medicine, National Heart & Lung Institute

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3409a.lyon Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Couch:2022:cvr/cvab210,
author = {Couch, LS and Fiedler, J and Chick, G and Clayton, R and Dries, E and Wienecke, LM and Fu, L and Fourre, J and Pandey, P and Derda, AA and Wang, BX and Jabbour, R and Shanmuganathan, M and Wright, P and Lyon, AR and Terracciano, CM and Thum, T and Harding, SE},
doi = {cvr/cvab210},
journal = {Cardiovascular Research},
pages = {1758--1770},
title = {Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure},
url = {http://dx.doi.org/10.1093/cvr/cvab210},
volume = {118},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and absence of coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal) cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavβ subunit), RGS4 (regulator of G-protein signalling 4) and G-protein subunit Gβ (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitise the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future. TRANSLATIONAL PERSPECTIVE: TTS-associated miRs have the potential to be active players predisposing to TTS. Feasibly, their measurement in recovered TTS patients during subsequent peri
AU  - Couch,LS
AU  - Fiedler,J
AU  - Chick,G
AU  - Clayton,R
AU  - Dries,E
AU  - Wienecke,LM
AU  - Fu,L
AU  - Fourre,J
AU  - Pandey,P
AU  - Derda,AA
AU  - Wang,BX
AU  - Jabbour,R
AU  - Shanmuganathan,M
AU  - Wright,P
AU  - Lyon,AR
AU  - Terracciano,CM
AU  - Thum,T
AU  - Harding,SE
DO  - cvr/cvab210
EP  - 1770
PY  - 2022///
SN  - 0008-6363
SP  - 1758
TI  - Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure
T2  - Cardiovascular Research
UR  - http://dx.doi.org/10.1093/cvr/cvab210
UR  - https://www.ncbi.nlm.nih.gov/pubmed/34155498
UR  - http://hdl.handle.net/10044/1/90763
VL  - 118
ER  -
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