Unravelling Atrioventricular Block Risk in Inflammatory Diseases: Systemic Inflammation Acutely Delays Atrioventricular Conduction via a Cytokine-Mediated Inhibition of Connexin43 Expression

Autor: Alessandro Frosali, Decoroso Verrengia, Alessandra Gamberucci, Mohamed Boutjdir, Francesca Vanni, Franco Laghi-Pasini, Aleksander Dokollari, Pier Leopoldo Capecchi, Alessandra Cartocci, Maurizio Acampa, Nabil El-Sherif, Claudio Nanni, Antonio D'Errico, Pietro Enea Lazzerini, Ujala Srivastava, Iacopo Bertolozzi, Anna Cantore, Michael Cupelli, Fabio Salvadori, Viola Salvini, Riccardo Accioli, Massimo Maccherini
Rok vydání: 2021
Předmět:
medicine.medical_treatment
Guinea Pigs
Arrhythmias
Systemic inflammation
Peripheral blood mononuclear cell
In vivo
medicine
Diseases of the circulatory (Cardiovascular) system
Animals
Humans
Arrhythmia and Electrophysiology
Interleukin 6
Atrioventricular Block
Original Research
Inflammation
systemic inflammation
atrioventricular conduction
biology
business.industry
Interleukin-6
Interleukin
cardiac electrical remodelling
Ion Channels/Membrane Transport
medicine.disease
Atrioventricular node
connexin43
PR‐interval
Cytokine
medicine.anatomical_structure
interleukin‐6
Growth Factors/Cytokines
RC666-701
Connexin 43
Immunology
atrioventricular blocks
biology.protein
cardiovascular system
Atrioventricular Node
Leukocytes
Mononuclear
Cytokines
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Atrioventricular block
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 21 (2021)
ISSN: 2047-9980
Popis: Background Recent data suggest that systemic inflammation can negatively affect atrioventricular conduction, regardless of acute cardiac injury. Indeed, gap‐junctions containing connexin43 coupling cardiomyocytes and inflammation‐related cells (macrophages) are increasingly recognized as important factors regulating the conduction in the atrioventricular node. The aim of this study was to evaluate the acute impact of systemic inflammatory activation on atrioventricular conduction, and elucidate underlying mechanisms. Methods and Results We analyzed: (1) the PR‐interval in patients with inflammatory diseases of different origins during active phase and recovery, and its association with inflammatory markers; (2) the existing correlation between connexin43 expression in the cardiac tissue and peripheral blood mononuclear cells (PBMC), and the changes occurring in patients with inflammatory diseases over time; (3) the acute effects of interleukin(IL)‐6 on atrioventricular conduction in an in vivo animal model, and on connexin43 expression in vitro. In patients with elevated C‐reactive protein levels, atrioventricular conduction indices are increased, but promptly normalized in association with inflammatory markers reduction, particularly IL‐6. In these subjects, connexin43 expression in PBMC, which is correlative of that measured in the cardiac tissue, inversely associated with IL‐6 changes. Moreover, direct IL‐6 administration increased atrioventricular conduction indices in vivo in a guinea pig model, and IL‐6 incubation in both cardiomyocytes and macrophages in culture, significantly reduced connexin43 proteins expression. Conclusions The data evidence that systemic inflammation can acutely worsen atrioventricular conduction, and that IL‐6‐induced down‐regulation of cardiac connexin43 is a mechanistic pathway putatively involved in the process. Though reversible, these alterations could significantly increase the risk of severe atrioventricular blocks during active inflammatory processes.
Databáze: OpenAIRE
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