Remodeling of gap junctions in mouse hearts hypertrophied by forced retinoic acid signaling

Autor: Habo J. Jongsma, Rob F. Wiegerinck, Jacques M.T. de Bakker, Harold V.M. van Rijen, Toon A.B. van Veen, Tobias Opthof, Sophie Clément, Melissa C. Colbert
Přispěvatelé: Cardiology, Amsterdam Cardiovascular Sciences
Jazyk: angličtina
Rok vydání: 2002
Předmět:
Myocardium/pathology
Receptors
Retinoic Acid
Retinoic acid
Connexin
Cadherins/metabolism
ddc:616.07
Ventricular tachycardia
Biomarkers/analysis
Muscle hypertrophy
chemistry.chemical_compound
Electrocardiography
Mice
beta Catenin
Cytoskeletal Proteins/metabolism
Gap junction
Gap Junctions
Dilated cardiomyopathy
Organ Size
Cadherins
Actins/metabolism
cardiovascular system
Cardiomegaly/pathology
Tretinoin/metabolism
Cardiology and Cardiovascular Medicine
Gap Junctions/metabolism
Signal Transduction
Genetically modified mouse
medicine.medical_specialty
Blotting
Western
Down-Regulation
Cardiomegaly
Tretinoin
Mice
Transgenic
Receptors
Retinoic Acid/genetics/metabolism
Internal medicine
medicine
Animals
Trans-Activators/metabolism
Molecular Biology
Myocardium
Body Weight
medicine.disease
Actins
Electric Stimulation
Retinoic acid receptor
Cytoskeletal Proteins
Endocrinology
chemistry
Connexin 43
Trans-Activators
Connexin 43/metabolism
Biomarkers
Zdroj: Journal of Molecular and Cellular Cardiology, Vol. 34, No 10 (2002) pp. 1411-1423
Journal of molecular and cellular cardiology, 34(10), 1411-1423. Academic Press Inc.
ISSN: 0022-2828
DOI: 10.1006/jmcc.2002.2102
Popis: T. A. B. VAN VEEN, H. V. M. VAN RIJEN, R. F. WIEGERINCK, T. OPTHOF, M. C. COLBERT, S. CLEMENT. J. M. T. DE BAKKER AND H, J. JONGSMA. Remodeling of Gap Junctions in Mouse Hearts Hypertrophied by Forced Retinoic Acid Signaling. Journal of Molecular and Cellular Cardiology (2002) 34, 1411-1423. Background: beta-MHC-hRARalpha transgenic mice express a constitutively active (truncated) form of the human retinoic acid receptor which triggers development of dilated cardiomyopathy. in those hearts, we studied expression of gap junction proteins in relation to electrical impulse propagation. Methods and Results: As compared to wildtype mice, hearts of 4-6 month old mice with 7-12 inserted hRARalpha copies are marked by an increased heart weight/body weight- and heart weight/tibia length ratio. 3-extremity lead ECGs revealed prolongation of the Q-i interval suggesting delayed ventricular activation. Mapping of electrical activity of epi- and endocardial left ventricular free wall revealed activation delay, increased heterogeneity in conduction and regional conduction block. Ventricular tachycardia's did not occur spontaneously nor could be induced by ventricular pacing. Immunohistochemical analysis showed profound and heterogeneous redistribution and down-regulation of the gap junction protein connexin43 (Cx43) in the left ventricular free wall. Here, hRARalpha expression induced re-expression of the hypertrophic markers alpha-skeletal actin and beta-MHC, and in 3 out of 10 severely affected mice, re-expression of Cx40. Concomitant with changes in expression/distribution of Cx43, changes in expression and distribution of beta-catenin and N-cadherin (two other intercalated disk associated proteins) were observed. Conclusions: beta-MHC-hRARalpha transgenic hearts show heterogeneous re-expression of (early) sarcomeric genes while expression of connexin43, N-cadherin and beta-catenin is down-regulated. We postulate that the resulting aberrant ventricular activation does not trigger development of lethal arrhythmias due to the small size of remaining healthy ventricular tissue where the transgene is not expressed. (C) 2002 Published by Elsevier Science Ltd
Databáze: OpenAIRE
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