Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation

S. Dhein, S. Rothe, A. Busch, D. M. Rojas Gomez, A. Boldt, A. Reutemann, T. Seidel, A. Salameh, B. Pfannmüller, A. Rastan, M. Kostelka, F. W. Mohr

Resultado de la investigación: Article

25 Citas (Scopus)

Resumen

BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day -1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs.

Idioma originalEnglish
Páginas (desde-hasta)607-616
Número de páginas10
PublicaciónBritish Journal of Pharmacology
Volumen164
N.º2 B
DOI
EstadoPublished - 1 sep 2011

Huella dactilar

Connexin 43
Metoprolol
Gap Junctions
Atrial Fibrillation
Therapeutics
Connexins
Electrodes
Western Blotting
Pharmacology

ASJC Scopus subject areas

  • Pharmacology

Citar esto

Dhein, S. ; Rothe, S. ; Busch, A. ; Rojas Gomez, D. M. ; Boldt, A. ; Reutemann, A. ; Seidel, T. ; Salameh, A. ; Pfannmüller, B. ; Rastan, A. ; Kostelka, M. ; Mohr, F. W. / Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation. En: British Journal of Pharmacology. 2011 ; Vol. 164, N.º 2 B. pp. 607-616.
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title = "Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation",
abstract = "BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day -1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs.",
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author = "S. Dhein and S. Rothe and A. Busch and {Rojas Gomez}, {D. M.} and A. Boldt and A. Reutemann and T. Seidel and A. Salameh and B. Pfannm{\"u}ller and A. Rastan and M. Kostelka and Mohr, {F. W.}",
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Dhein, S, Rothe, S, Busch, A, Rojas Gomez, DM, Boldt, A, Reutemann, A, Seidel, T, Salameh, A, Pfannmüller, B, Rastan, A, Kostelka, M & Mohr, FW 2011, 'Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation', British Journal of Pharmacology, vol. 164, n.º 2 B, pp. 607-616. https://doi.org/10.1111/j.1476-5381.2011.01460.x

Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation. / Dhein, S.; Rothe, S.; Busch, A.; Rojas Gomez, D. M.; Boldt, A.; Reutemann, A.; Seidel, T.; Salameh, A.; Pfannmüller, B.; Rastan, A.; Kostelka, M.; Mohr, F. W.

En: British Journal of Pharmacology, Vol. 164, N.º 2 B, 01.09.2011, p. 607-616.

Resultado de la investigación: Article

TY - JOUR

T1 - Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation

AU - Dhein, S.

AU - Rothe, S.

AU - Busch, A.

AU - Rojas Gomez, D. M.

AU - Boldt, A.

AU - Reutemann, A.

AU - Seidel, T.

AU - Salameh, A.

AU - Pfannmüller, B.

AU - Rastan, A.

AU - Kostelka, M.

AU - Mohr, F. W.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day -1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs.

AB - BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day -1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs.

KW - β-blocker

KW - anisotropy

KW - atrial fibrillation

KW - conduction velocity

KW - connexin40

KW - connexin43

KW - gap junction

KW - metoprolol

UR - http://www.scopus.com/inward/record.url?scp=80052250729&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.2011.01460.x

DO - 10.1111/j.1476-5381.2011.01460.x

M3 - Article

C2 - 21542828

AN - SCOPUS:80052250729

VL - 164

SP - 607

EP - 616

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2 B

ER -