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Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice

Background: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). Methods: JDP2-overexpression was...

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Autores principales: Parahuleva, Mariana S., Kockskämper, Jens, Heger, Jacqueline, Grimm, Wolfram, Scherer, Anna, Bühler, Sarah, Kreutz, Julian, Schulz, Rainer, Euler, Gerhild
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731172/
https://www.ncbi.nlm.nih.gov/pubmed/33265909
http://dx.doi.org/10.3390/ijms21239095
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author Parahuleva, Mariana S.
Kockskämper, Jens
Heger, Jacqueline
Grimm, Wolfram
Scherer, Anna
Bühler, Sarah
Kreutz, Julian
Schulz, Rainer
Euler, Gerhild
author_facet Parahuleva, Mariana S.
Kockskämper, Jens
Heger, Jacqueline
Grimm, Wolfram
Scherer, Anna
Bühler, Sarah
Kreutz, Julian
Schulz, Rainer
Euler, Gerhild
author_sort Parahuleva, Mariana S.
collection PubMed
description Background: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). Methods: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. Results: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. Conclusion: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.
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spelling pubmed-77311722020-12-12 Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice Parahuleva, Mariana S. Kockskämper, Jens Heger, Jacqueline Grimm, Wolfram Scherer, Anna Bühler, Sarah Kreutz, Julian Schulz, Rainer Euler, Gerhild Int J Mol Sci Article Background: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). Methods: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. Results: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. Conclusion: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF. MDPI 2020-11-30 /pmc/articles/PMC7731172/ /pubmed/33265909 http://dx.doi.org/10.3390/ijms21239095 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Parahuleva, Mariana S.
Kockskämper, Jens
Heger, Jacqueline
Grimm, Wolfram
Scherer, Anna
Bühler, Sarah
Kreutz, Julian
Schulz, Rainer
Euler, Gerhild
Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title_full Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title_fullStr Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title_full_unstemmed Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title_short Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice
title_sort structural, pro-inflammatory and calcium handling remodeling underlies spontaneous onset of paroxysmal atrial fibrillation in jdp2-overexpressing mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731172/
https://www.ncbi.nlm.nih.gov/pubmed/33265909
http://dx.doi.org/10.3390/ijms21239095
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