Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes. / Mesirca, Pietro; Nakao, Shu; Nissen, Sarah Dalgas; Forte, Gabriella; Anderson, Cali; Trussell, Tariq; Li, Jue; Cox, Charlotte; Zi, Min; Logantha, Sunil; Yaar, Sana; Cartensen, Helena; Bidaud, Isabelle; Stuart, Luke; Soattin, Luca; Morris, Gwilym M.; Da Costa Martins, Paula A.; Cartwright, Elizabeth J.; Oceandy, Delvac; Mangoni, Matteo E.; Jespersen, Thomas; Buhl, Rikke; Dobrzynski, Halina; Boyett, Mark R.; D'Souza, Alicia.

I: Circulation Research, Bind 129, Nr. 1, 2021, s. E1-E20.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Mesirca, P, Nakao, S, Nissen, SD, Forte, G, Anderson, C, Trussell, T, Li, J, Cox, C, Zi, M, Logantha, S, Yaar, S, Cartensen, H, Bidaud, I, Stuart, L, Soattin, L, Morris, GM, Da Costa Martins, PA, Cartwright, EJ, Oceandy, D, Mangoni, ME, Jespersen, T, Buhl, R, Dobrzynski, H, Boyett, MR & D'Souza, A 2021, 'Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes', Circulation Research, bind 129, nr. 1, s. E1-E20. https://doi.org/10.1161/CIRCRESAHA.119.316386

APA

Mesirca, P., Nakao, S., Nissen, S. D., Forte, G., Anderson, C., Trussell, T., Li, J., Cox, C., Zi, M., Logantha, S., Yaar, S., Cartensen, H., Bidaud, I., Stuart, L., Soattin, L., Morris, G. M., Da Costa Martins, P. A., Cartwright, E. J., Oceandy, D., ... D'Souza, A. (2021). Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes. Circulation Research, 129(1), E1-E20. https://doi.org/10.1161/CIRCRESAHA.119.316386

Vancouver

Mesirca P, Nakao S, Nissen SD, Forte G, Anderson C, Trussell T o.a. Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes. Circulation Research. 2021;129(1):E1-E20. https://doi.org/10.1161/CIRCRESAHA.119.316386

Author

Mesirca, Pietro ; Nakao, Shu ; Nissen, Sarah Dalgas ; Forte, Gabriella ; Anderson, Cali ; Trussell, Tariq ; Li, Jue ; Cox, Charlotte ; Zi, Min ; Logantha, Sunil ; Yaar, Sana ; Cartensen, Helena ; Bidaud, Isabelle ; Stuart, Luke ; Soattin, Luca ; Morris, Gwilym M. ; Da Costa Martins, Paula A. ; Cartwright, Elizabeth J. ; Oceandy, Delvac ; Mangoni, Matteo E. ; Jespersen, Thomas ; Buhl, Rikke ; Dobrzynski, Halina ; Boyett, Mark R. ; D'Souza, Alicia. / Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes. I: Circulation Research. 2021 ; Bind 129, Nr. 1. s. E1-E20.

Bibtex

@article{26d601e91e3f4754b7f93b55f846c7ca,
title = "Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes",
abstract = "Rationale: Athletes present with atrioventricular node dysfunction manifesting as atrioventricular block. This can necessitate electronic pacemaker implantation, known to be more frequent in athletes with a long training history. Objective: Atrioventricular block in athletes is attributed to high vagal tone. Here, we investigated the alternative hypothesis that electrical remodeling of the atrioventricular node is responsible. Methods and Results: Radiotelemetry ECG data and atrioventricular node biopsies were collected in sedentary and trained Standardbred racehorses, a large-animal model of the athlete's heart. Trained horses presented with longer PR intervals (that persisted under complete autonomic block) versus sedentary horses, concomitant with reduced expression of key ion channels involved in atrioventricular node conduction: L-type Ca2+channel subunit CaV1.2 and HCN4 (hyperpolarization-activated cyclic nucleotide-gated channel 4). Atrioventricular node electrophysiology was explored further in mice; prolongation of the PR interval (in vivo and ex vivo), Wenckebach cycle length, and atrioventricular node refractory period were observed in mice trained by swimming versus sedentary mice. Transcriptional profiling in laser-capture microdissected atrioventricular node revealed striking reduction in pacemaking ion channels in trained mice, translating into protein downregulation of CaV1.2 and HCN4. Correspondingly, patch-clamp recordings in isolated atrioventricular node myocytes demonstrated a training-induced reduction in ICa,Land Ifdensity that likely contributed to the observed lower frequency of action potential firing in trained cohorts. MicroRNA (miR) profiling and in vitro studies revealed miR-211-5p and miR-432 as direct regulators of CaV1.2 and HCN4. In vivo miRs suppression or detraining restored training-induced PR prolongation and ion channel remodeling. Conclusions: Training-induced atrioventricular node dysfunction is underscored by likely miR-mediated transcriptional remodeling that translates into reduced current density of key ionic currents involved in impulse generation and conduction. We conclude that electrical remodeling is a key mechanism underlying atrioventricular block in athletes.",
keywords = "atrioventricular block, cardiac electrophysiology, exercise, ion channels, microRNAs",
author = "Pietro Mesirca and Shu Nakao and Nissen, {Sarah Dalgas} and Gabriella Forte and Cali Anderson and Tariq Trussell and Jue Li and Charlotte Cox and Min Zi and Sunil Logantha and Sana Yaar and Helena Cartensen and Isabelle Bidaud and Luke Stuart and Luca Soattin and Morris, {Gwilym M.} and {Da Costa Martins}, {Paula A.} and Cartwright, {Elizabeth J.} and Delvac Oceandy and Mangoni, {Matteo E.} and Thomas Jespersen and Rikke Buhl and Halina Dobrzynski and Boyett, {Mark R.} and Alicia D'Souza",
note = "Publisher Copyright: {\textcopyright} 2021 Lippincott Williams and Wilkins. All rights reserved.",
year = "2021",
doi = "10.1161/CIRCRESAHA.119.316386",
language = "English",
volume = "129",
pages = "E1--E20",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "AHA/ASA",
number = "1",

}

RIS

TY - JOUR

T1 - Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes

AU - Mesirca, Pietro

AU - Nakao, Shu

AU - Nissen, Sarah Dalgas

AU - Forte, Gabriella

AU - Anderson, Cali

AU - Trussell, Tariq

AU - Li, Jue

AU - Cox, Charlotte

AU - Zi, Min

AU - Logantha, Sunil

AU - Yaar, Sana

AU - Cartensen, Helena

AU - Bidaud, Isabelle

AU - Stuart, Luke

AU - Soattin, Luca

AU - Morris, Gwilym M.

AU - Da Costa Martins, Paula A.

AU - Cartwright, Elizabeth J.

AU - Oceandy, Delvac

AU - Mangoni, Matteo E.

AU - Jespersen, Thomas

AU - Buhl, Rikke

AU - Dobrzynski, Halina

AU - Boyett, Mark R.

AU - D'Souza, Alicia

N1 - Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Rationale: Athletes present with atrioventricular node dysfunction manifesting as atrioventricular block. This can necessitate electronic pacemaker implantation, known to be more frequent in athletes with a long training history. Objective: Atrioventricular block in athletes is attributed to high vagal tone. Here, we investigated the alternative hypothesis that electrical remodeling of the atrioventricular node is responsible. Methods and Results: Radiotelemetry ECG data and atrioventricular node biopsies were collected in sedentary and trained Standardbred racehorses, a large-animal model of the athlete's heart. Trained horses presented with longer PR intervals (that persisted under complete autonomic block) versus sedentary horses, concomitant with reduced expression of key ion channels involved in atrioventricular node conduction: L-type Ca2+channel subunit CaV1.2 and HCN4 (hyperpolarization-activated cyclic nucleotide-gated channel 4). Atrioventricular node electrophysiology was explored further in mice; prolongation of the PR interval (in vivo and ex vivo), Wenckebach cycle length, and atrioventricular node refractory period were observed in mice trained by swimming versus sedentary mice. Transcriptional profiling in laser-capture microdissected atrioventricular node revealed striking reduction in pacemaking ion channels in trained mice, translating into protein downregulation of CaV1.2 and HCN4. Correspondingly, patch-clamp recordings in isolated atrioventricular node myocytes demonstrated a training-induced reduction in ICa,Land Ifdensity that likely contributed to the observed lower frequency of action potential firing in trained cohorts. MicroRNA (miR) profiling and in vitro studies revealed miR-211-5p and miR-432 as direct regulators of CaV1.2 and HCN4. In vivo miRs suppression or detraining restored training-induced PR prolongation and ion channel remodeling. Conclusions: Training-induced atrioventricular node dysfunction is underscored by likely miR-mediated transcriptional remodeling that translates into reduced current density of key ionic currents involved in impulse generation and conduction. We conclude that electrical remodeling is a key mechanism underlying atrioventricular block in athletes.

AB - Rationale: Athletes present with atrioventricular node dysfunction manifesting as atrioventricular block. This can necessitate electronic pacemaker implantation, known to be more frequent in athletes with a long training history. Objective: Atrioventricular block in athletes is attributed to high vagal tone. Here, we investigated the alternative hypothesis that electrical remodeling of the atrioventricular node is responsible. Methods and Results: Radiotelemetry ECG data and atrioventricular node biopsies were collected in sedentary and trained Standardbred racehorses, a large-animal model of the athlete's heart. Trained horses presented with longer PR intervals (that persisted under complete autonomic block) versus sedentary horses, concomitant with reduced expression of key ion channels involved in atrioventricular node conduction: L-type Ca2+channel subunit CaV1.2 and HCN4 (hyperpolarization-activated cyclic nucleotide-gated channel 4). Atrioventricular node electrophysiology was explored further in mice; prolongation of the PR interval (in vivo and ex vivo), Wenckebach cycle length, and atrioventricular node refractory period were observed in mice trained by swimming versus sedentary mice. Transcriptional profiling in laser-capture microdissected atrioventricular node revealed striking reduction in pacemaking ion channels in trained mice, translating into protein downregulation of CaV1.2 and HCN4. Correspondingly, patch-clamp recordings in isolated atrioventricular node myocytes demonstrated a training-induced reduction in ICa,Land Ifdensity that likely contributed to the observed lower frequency of action potential firing in trained cohorts. MicroRNA (miR) profiling and in vitro studies revealed miR-211-5p and miR-432 as direct regulators of CaV1.2 and HCN4. In vivo miRs suppression or detraining restored training-induced PR prolongation and ion channel remodeling. Conclusions: Training-induced atrioventricular node dysfunction is underscored by likely miR-mediated transcriptional remodeling that translates into reduced current density of key ionic currents involved in impulse generation and conduction. We conclude that electrical remodeling is a key mechanism underlying atrioventricular block in athletes.

KW - atrioventricular block

KW - cardiac electrophysiology

KW - exercise

KW - ion channels

KW - microRNAs

U2 - 10.1161/CIRCRESAHA.119.316386

DO - 10.1161/CIRCRESAHA.119.316386

M3 - Journal article

C2 - 33849278

AN - SCOPUS:85108363022

VL - 129

SP - E1-E20

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 1

ER -

ID: 273642702