Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias

Mohamed Boulaksil, Stephan K G Winckels, Markus A. Engelen, Mra Stein, Toon A B Van Veen, John A. Jansen, André C. Linnenbank, Marti F A Bierhuizen, W. Antoinette Groenewegen, Matthijs F M Van Oosterhout, Johannes H. Kirkels, Nicolaas De Jonge, A. Varró, Marc A. Vos, Jacques M T De Bakker, Harold V M Van Rijen

Research output: Contribution to journalArticle

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Abstract

Aims Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. Methods results and Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-)and results documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT-patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44 TAC and 0 sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. ConclusionHeterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias.

Original languageEnglish
Pages (from-to)913-921
Number of pages9
JournalEuropean Journal of Heart Failure
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Connexin 43
Cardiac Arrhythmias
Constriction
Heart Failure
Fibrosis
Gap Junctions
Sudden Cardiac Death
Cell Size
Tachycardia
Echocardiography
Myocardium
Biopsy
Pressure
Mortality

Keywords

  • Arrhythmia
  • Electrophysiology
  • Gap junctions
  • Heart failure
  • Sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Boulaksil, M., Winckels, S. K. G., Engelen, M. A., Stein, M., Van Veen, T. A. B., Jansen, J. A., ... Van Rijen, H. V. M. (2010). Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. European Journal of Heart Failure, 12(9), 913-921. https://doi.org/10.1093/eurjhf/hfq092

Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. / Boulaksil, Mohamed; Winckels, Stephan K G; Engelen, Markus A.; Stein, Mra; Van Veen, Toon A B; Jansen, John A.; Linnenbank, André C.; Bierhuizen, Marti F A; Groenewegen, W. Antoinette; Van Oosterhout, Matthijs F M; Kirkels, Johannes H.; De Jonge, Nicolaas; Varró, A.; Vos, Marc A.; De Bakker, Jacques M T; Van Rijen, Harold V M.

In: European Journal of Heart Failure, Vol. 12, No. 9, 09.2010, p. 913-921.

Research output: Contribution to journalArticle

Boulaksil, M, Winckels, SKG, Engelen, MA, Stein, M, Van Veen, TAB, Jansen, JA, Linnenbank, AC, Bierhuizen, MFA, Groenewegen, WA, Van Oosterhout, MFM, Kirkels, JH, De Jonge, N, Varró, A, Vos, MA, De Bakker, JMT & Van Rijen, HVM 2010, 'Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias', European Journal of Heart Failure, vol. 12, no. 9, pp. 913-921. https://doi.org/10.1093/eurjhf/hfq092
Boulaksil, Mohamed ; Winckels, Stephan K G ; Engelen, Markus A. ; Stein, Mra ; Van Veen, Toon A B ; Jansen, John A. ; Linnenbank, André C. ; Bierhuizen, Marti F A ; Groenewegen, W. Antoinette ; Van Oosterhout, Matthijs F M ; Kirkels, Johannes H. ; De Jonge, Nicolaas ; Varró, A. ; Vos, Marc A. ; De Bakker, Jacques M T ; Van Rijen, Harold V M. / Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias. In: European Journal of Heart Failure. 2010 ; Vol. 12, No. 9. pp. 913-921.
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abstract = "Aims Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. Methods results and Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-)and results documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT-patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44 TAC and 0 sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. ConclusionHeterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias.",
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T1 - Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias

AU - Boulaksil, Mohamed

AU - Winckels, Stephan K G

AU - Engelen, Markus A.

AU - Stein, Mra

AU - Van Veen, Toon A B

AU - Jansen, John A.

AU - Linnenbank, André C.

AU - Bierhuizen, Marti F A

AU - Groenewegen, W. Antoinette

AU - Van Oosterhout, Matthijs F M

AU - Kirkels, Johannes H.

AU - De Jonge, Nicolaas

AU - Varró, A.

AU - Vos, Marc A.

AU - De Bakker, Jacques M T

AU - Van Rijen, Harold V M

PY - 2010/9

Y1 - 2010/9

N2 - Aims Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. Methods results and Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-)and results documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT-patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44 TAC and 0 sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. ConclusionHeterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias.

AB - Aims Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure (CHF). To investigate determinants of the increased arrhythmogenic susceptibility, we studied cardiac remodelling and arrhythmogenicity in CHF patients and in a mouse model of chronic pressure overload. Methods results and Clinical and (immuno)histological data of myocardial biopsies from CHF patients with (VT+) and without (VT-)and results documented ventricular arrhythmia were compared with controls. In CHF patients, ejection fraction was decreased and QRS duration was increased. Cell size and interstitial fibrosis were increased, but Connexin43 (Cx43) levels, the most abundant gap junction in ventricular myocardium, were unchanged. No differences were found between VT+ and VT-patients, except for the distribution pattern of Cx43, which was significantly more heterogeneous in VT+. Mice were subjected to transverse aortic constriction (TAC) or sham operated. At 16 weeks, cardiac function was determined by echocardiography and epicardial ventricular activation mapping was performed. Transverse aortic constriction mice had decreased fractional shortening and prolonged QRS duration. Right ventricular conduction velocity was reduced, and polymorphic VTs were induced in 44 TAC and 0 sham mice. Interstitial fibrosis was increased and Cx43 quantity was unchanged in TAC mice with and without arrhythmias. Similar to CHF patients, heterogeneous Cx43 distribution was significantly associated with arrhythmias in TAC mice and with spatial heterogeneity of impulse conduction. ConclusionHeterogeneous Cx43 expression during CHF is associated with dispersed impulse conduction and may underlie enhanced susceptibility to ventricular tachyarrhythmias.

KW - Arrhythmia

KW - Electrophysiology

KW - Gap junctions

KW - Heart failure

KW - Sudden death

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