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Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/74142

Type: Journal article
Title: IGF-2R-mediated signaling results in hypertrophy of cultured cardiomyocytes from fetal sheep
Author: Wang, Kimberley Choon Wen
Brooks, Douglas Alexander
Botting, Kimberley Jae
Morrison, Janna Leigh
Citation: Biology of Reproduction, 2012; 86(6):183, 1-8
Publisher: Society for the Study of Reproduction
Issue Date: 2012
ISSN: 0006-3363
1529-7268
School/Discipline: School of Medical Sciences Office
Statement of
Responsibility: 
Kimberley C.W. Wang, Doug A. Brooks, Kimberley J. Botting and Janna L. Morrison
Abstract: Activation of the insulin-like growth factor-1 receptor (IGF-1R) is known to play a role in cardiomyocyte hypertrophy. While IGF-2R is understood to be a clearance receptor for IGF-2, there is also evidence that it may play a role in the induction of pathological cardiomyocyte hypertrophy. It is not known whether IGF-2R activates cardiomyocyte hypertrophy during growth of the fetal heart. Fetal sheep hearts (125 ± 0.4 days gestation) were dissected, and the cardiomyocytes isolated from the left and right ventricles for culturing. Cultured cardiomyocytes were treated with either LONG R3IGF-1, an IGF-1R agonist; picropodophyllin, an IGF-1R autophosphorylation inhibitor; U0126, an inhibitor of extracellular signal-regulated protein kinase (ERK); Leu27IGF-2, an IGF-2R agonist; Gö6976, a protein kinase C inhibitor; KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII); or KN-92, an L-type calcium channel inhibitor and negative control for KN-93. The cross-sectional area of cultured cardiomyocytes was determined relative to control cardiomyocytes treated with serum-free culture medium. IGF-1R and IGF-2R activation each resulted in ERK signaling, but IGF-2R activation alone induced CaMKII signaling, resulting in hypertrophy of cardiomyocytes in the late gestation sheep fetus. These data suggest that changes in the intrauterine environment that result in increased cardiac IGF-2R may also lead to cardiomyocyte hypertrophy in the fetus and potentially an increased risk of cardiovascular disease in adult life.
Keywords: Cell culture; developmental origins of health and disease; ovine; sheep
Rights: © 2012 by the Society for the Study of Reproduction
RMID: 0020121164
DOI: 10.1095/biolreprod.112.100388
Appears in Collections:Medical Sciences publications
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