Early onset heart failure in transgenic mice with dilated cardiomyopathy

D. Greg Hall, Gregory E. Morley, Dhananjay Vaidya, Ard Mary, Thomas R. Kimball, Sandra A. Witt, Melissa C. Colbert

Research output: Contribution to journalArticle

Abstract

In children, dilated cardiomyopathy is due to a variety of etiologies and usually carries a grave prognosis. The purpose of the present study was to carefully follow the progression of events leading to cardiac dilatation and congestive heart failure in a dilated cardiomyopathy model in neonatal and juvenile mice. These initial steps are often not well characterized. Furthermore, the loss of gap junctions and reduced electrical coupling of cardiomyocytes frequently found in human cardiomyopathies are also observed in these early stages. By 2 wk of age, molecular markers associated with hypertrophy were already altered. Cardiomyocyte hypertrophy, reduced connexin43 expression, and decreased conduction velocity were apparent by 4 wk, before overt cardiac dysfunction (decreased shortening fraction and chamber remodeling) that was not present until 12 wk of age. Our results show that in this model cardiomyopathic changes are present by 2 wk after birth and progress rapidly during the subsequent 2 postnatal weeks. Combined with the observations of other models of heart disease, we suggest that the first 2 wk of postnatal life are absolutely critical for normal cardiac development, and events that perturb homeostasis during this period determine whether the heart will continue to develop normally. These animals exhibit early symptoms of disease including reduced connexin43 and conduction defects before impaired cardiac function and demonstrate for the first time a temporal association between decreased connexin43 levels and the initiation of a contractility deficit that ends in heart failure.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalPediatric research
Volume48
Issue number1
DOIs
StatePublished - Jul 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Hall, D. G., Morley, G. E., Vaidya, D., Mary, A., Kimball, T. R., Witt, S. A., & Colbert, M. C. (2000). Early onset heart failure in transgenic mice with dilated cardiomyopathy. Pediatric research, 48(1), 36-42. https://doi.org/10.1203/00006450-200007000-00009