Cardiomyocyte Hypertrophy in Arrhythmogenic Cardiomyopathy.

Autor:	Gerçek M; Institutes for Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany., Gerçek M; Institutes for Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany., Kant S; Institutes for Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany., Simsekyilmaz S; Institute of Pharmacology and Clinical Pharmacology, Heinrich Heine University, Düsseldorf, Germany., Kassner A; Heart and Diabetes Center North Rhine-Westphalia, Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Bad Oeynhausen, Germany., Milting H; Heart and Diabetes Center North Rhine-Westphalia, Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Bad Oeynhausen, Germany., Liehn EA; Institute for Molecular Cardiovascular Research and Interdisciplinary Center for Clinical Research Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany., Leube RE; Institutes for Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany., Krusche CA; Institutes for Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany. Electronic address: ckrusche@ukaachen.de.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2017 Apr; Vol. 187 (4), pp. 752-766. Date of Electronic Publication: 2017 Feb 07.
DOI:	10.1016/j.ajpath.2016.12.018
Abstrakt:	Arrhythmogenic cardiomyopathy (AC) is a hereditary disease leading to sudden cardiac death or heart failure. AC pathology is characterized by cardiomyocyte loss and replacement fibrosis. Our goal was to determine whether cardiomyocytes respond to AC progression by pathological hypertrophy. To this end, we examined tissue samples from AC patients with end-stage heart failure and tissue samples that were collected at different disease stages from desmoglein 2-mutant mice, a well characterized AC model. We find that cardiomyocyte diameters are significantly increased in right ventricles of AC patients. Increased mRNA expression of the cardiac stress marker natriuretic peptide B is also observed in the right ventricle of AC patients. Elevated myosin heavy chain 7 mRNA expression is detected in left ventricles. In desmoglein 2-mutant mice, cardiomyocyte diameters are normal during the concealed disease phase but increase significantly after acute disease onset on cardiomyocyte death and fibrotic myocardial remodeling. Hypertrophy progresses further during the chronic disease stage. In parallel, mRNA expression of myosin heavy chain 7 and natriuretic peptide B is up-regulated in both ventricles with right ventricular preference. Calcineurin/nuclear factor of activated T cells (Nfat) signaling, which is linked to pathological hypertrophy, is observed during AC progression, as evidenced by Nfatc2 and Nfatc3 mRNA in cardiomyocytes and increased mRNA of the Nfat target regulator of calcineurin 1. Taken together, we demonstrate that pathological hypertrophy occurs in AC and is secondary to cardiomyocyte loss and cardiac remodeling. (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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