Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction

Porrello, Enzo R., Bell, James R., Schertzer, Jonathan D., Curl, Claire L., McMullen, Julie R., Mellor, Kimberley M., Ritchie, Rebecca H., Lynch, Gordon S., Harrap, Stephen B., Thomas, Walter G. and Delbridge, Lea M. D. (2009) Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 296 3: R672-R680. doi:10.1152/ajpregu.90919.2008

Author Porrello, Enzo R.
Bell, James R.
Schertzer, Jonathan D.
Curl, Claire L.
McMullen, Julie R.
Mellor, Kimberley M.
Ritchie, Rebecca H.
Lynch, Gordon S.
Harrap, Stephen B.
Thomas, Walter G.
Delbridge, Lea M. D.
Title Heritable pathologic cardiac hypertrophy in adulthood is preceded by neonatal cardiac growth restriction
Journal name American Journal of Physiology: Regulatory, Integrative and Comparative Physiology   Check publisher's open access policy
ISSN 0363-6119
Publication date 2009-03
Year available 2009
Sub-type Article (original research)
DOI 10.1152/ajpregu.90919.2008
Volume 296
Issue 3
Start page R672
End page R680
Total pages 9
Place of publication College Park, MD, United States
Publisher American Physiologial Society
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060199 Biochemistry and Cell Biology not elsewhere classified
060602 Animal Physiology - Cell
110201 Cardiology (incl. Cardiovascular Diseases)
110903 Central Nervous System
Formatted abstract
The identification of genetic factors influencing cardiac growth independently of increased load is crucial to an understanding of the molecular and cellular basis of pathological cardiac hypertrophy. The central aim of this investigation was to determine how pathological hypertrophy in the adult can be linked with disturbances in cardiomyocyte growth and viability in early neonatal development. The hypertrophic heart rat (HHR) model is derived from the spontaneously hypertensive rat and exhibits marked cardiac hypertrophy, in the absence of a pressure load at maturity. Hearts were harvested from male HHR, and control strain normal heart rats (NHR), at different stages of postnatal development [neonatal (P2), 4 wk, 6 wk, 8 wk, 12 wk, 20 wk]. Isolated neonatal cardiomyocytes were prepared to evaluate cell size, number, and binucleation. At postnatal day 2, HHR hearts were considerably smaller than  control NHR (4.3 ± 0.2 vs. 5.0 ± 0.1 mg/g, P < 0.05). Cardiac growth restriction in the neonatal HHR was associated with reduced myocyte size (length and width) and an increased proportion of binucleated cardiomyocytes. Furthermore, the number of cardiomyocytes isolated from HHR neonatal hearts was significantly less (~  29%) than NHR. We also observe that growth stress in the neonate is associated with accentuated PI3K and suppressed MAPK activation, although these signaling  pathways are normalized in the adult heart exhibiting established hypertrophy. Thus, using the HHR model, we identified novel molecular and cellular mechanisms involving premature exit from the cell cycle, reduced cardiomyocyte endowment, and dysregulated trophic signaling during early development, which are implicated in the etiology of heritable cardiac hypertrophy in the adult. 
Keyword Cardiac development
Developmental origins of adult disease
Physiological and pathological cardiac hypertrophy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
ERA 2012 Admin Only
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 16:15:41 EST by Cameron Harris on behalf of School of Biomedical Sciences