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Rosenberg MA, Das S, Quintero Pinzon P, et al. A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation. J Atr Fibrillation. 2012;4(5):415doi: 10.4022/jafib.415.
Rosenberg, M. A., Das, S., Quintero Pinzon, P., Knight, A. C., Sosnovik, D. E., Ellinor, P. T., & Rosenzweig, A. (2012). A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation. Journal of atrial fibrillation, 4(5), 415. https://doi.org/10.4022/jafib.415
Rosenberg, Michael A, et al. "A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation." Journal of atrial fibrillation vol. 4,5 (2012): 415. doi: https://doi.org/10.4022/jafib.415
Rosenberg MA, Das S, Quintero Pinzon P, Knight AC, Sosnovik DE, Ellinor PT, Rosenzweig A. A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation. J Atr Fibrillation. 2012 Feb 02;4(5):415. doi: 10.4022/jafib.415. eCollection 2012. PMID: 28496713; PMCID: PMC3521534.
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J Atr Fibrillation. 2012 Feb 02;4(5):415. doi: 10.4022/jafib.415. eCollection 2012.

A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation.

Journal of atrial fibrillation

Michael A Rosenberg, Saumya Das, Pablo Quintero Pinzon, Ashley C Knight, David E Sosnovik, Patrick T Ellinor, Anthony Rosenzweig

Affiliations

  1. Cardiovascular Institute, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, CLS 9, Boston MA 02215.
  2. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston MA 02114.
  3. Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, Boston MA 02114.

PMID: 28496713 PMCID: PMC3521534 DOI: 10.4022/jafib.415

Abstract

Cardiac hypertrophy is a major risk factor for the development of atrial fibrillation (AF). However, there are few animal models of AF associated with cardiac hypertrophy. In this study, we describe the in vivo electrophysiological characteristics and histopathology of a mouse model of cardiac hypertrophy that develops AF. Myostatin is a well-known negative regulator of skeletal muscle growth that was recently found to additionally regulate cardiac muscle growth. Using cardiac-specific expression of the inhibitory myostatin pro-peptide, we generated transgenic (TG) mice with dominant-negative regulation of MSTN (DN-MSTN). One line (DN-MSTN TG13) displayed ventricular hypertrophy, as well as spontaneous AF on the surface electrocardiogram (ECG), and was further evaluated. DN-MSTN TG13 had normal systolic function, but displayed atrial enlargement on cardiac MRI, as well as atrial fibrosis histologically. Baseline ECG revealed an increased P wave duration and QRS interval compared with wild-type littermate (WT) mice. Seven of 19 DN-MSTN TG13 mice had spontaneous or inducible AF, while none of the WT mice had atrial arrhythmias (p<0.05). Connexin40 (Cx40) was decreased in DN-MSTN TG13 mice, even in the absence of AF or significant atrial fibrosis, raising the possibility that MSTN signaling may play a role in Cx40 down-regulation and the development of AF in this mouse model. In conclusion, DN-MSTN TG13 mice represent a novel model of AF, in which molecular changes including an initial loss of Cx40 are noted prior to fibrosis and the development of atrial arrhythmias.

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