Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/95443
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Type: Journal article
Title: IGF-2R-Gαq signaling and cardiac hypertrophy in the low-birth-weight lamb
Other Titles: IGF-2R-Galpha q signaling and cardiac hypertrophy in the low-birth-weight lamb
Author: Wang, K.
Tosh, D.
Zhang, S.
McMillen, I.
Duffield, J.
Brooks, D.
Morrison, J.
Citation: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2015; 308(7):R627-R635
Publisher: American Physiological Society
Issue Date: 2015
ISSN: 0363-6119
1522-1490
Statement of
Responsibility: 
Kimberley C. W. Wang, Darran N. Tosh, Song Zhang, I. Caroline McMillen, Jaime A. Duffield, Doug A. Brooks, and Janna L. Morrison
Abstract: The cardiac insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy in a heterotrimeric G protein receptor-coupled manner involving αq (Gαq) or αs (Gαs). We have previously shown increased left ventricular weight and cardiac IGF-2 and IGF-2R gene expression in low-birth-weight (LBW) compared with average-birth-weight (ABW) lambs. Here, we have investigated the cardiac expression of IGF-2 gene variants, the degree of histone acetylation, and the abundance of proteins in the IGF-2R downstream signaling pathway in ABW and LBW lambs. Samples from the left ventricle of ABW and LBW lambs were collected at 21 days of age. There was increased phospho-CaMKII protein with decreased HDAC 4 abundance in the LBW compared with ABW lambs. There was increased GATA 4 and decreased phospho-troponin I abundance in LBW compared with ABW lambs, which are markers of pathological cardiac hypertrophy and impaired or reduced contractility, respectively. There was increased histone acetylation of H3K9 at IGF-2R promoter and IGF-2R intron 2 differentially methylated region in the LBW lamb. In conclusion, histone acetylation of IGF-2R may lead to increased IGF-2R mRNA expression and subsequently mediate Gαq signaling early in life via CaMKII, resulting in an increased risk of left ventricular hypertrophy and cardiovascular disease in adult life.
Keywords: low birth weight; insulin-like growth factor 2 receptor; histone acetylation
Rights: Copyright © 2015 the American Physiological Society
RMID: 0030033464
DOI: 10.1152/ajpregu.00346.2014
Grant ID: http://purl.org/au-research/grants/nhmrc/349405
Appears in Collections:Medicine publications

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