Document Detail


Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus.
MedLine Citation:
PMID:  22930271     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vitro studies using rat and fetal sheep cardiomyocytes indicate that, in addition to its role as a clearance receptor, the insulin-like growth factor 2 receptor (IGF-2R) can induce cardiomyocyte hypertrophy. In the present study, we have determined the effect of specific activation of the IGF-2R in the heart of the late gestation fetus on cardiomyocyte development. Leu(27)IGF-2, an IGF-2R agonist, was infused into the fetal left circumflex coronary artery for 4 days beginning at 128.1 ± 0.4 days gestation. Ewes were humanely killed at 132.2 ± 1.2 days gestation (term, 150 days). Fetuses were delivered and hearts dissected to isolate the cardiomyocytes and to collect and snap-freeze tissue. Leu(27)IGF-2 infusion into the left circumflex coronary artery of fetal sheep increased the area of binucleated cardiomyocytes in the left, but not the right, ventricle. However, this infusion of Leu(27)IGF-2 did not change fetal weight, heart weight, blood pressure, blood gases or cardiomyocyte proliferation/binucleation. The increase in cardiomyocyte size in the Leu(27)IGF-2-infused group was associated with increased expression of proteins in the Gαs, but not the Gαq, signalling pathway. We concluded that infusion of Leu(27)IGF-2 into the left circumflex coronary artery causes cardiac IGF-2R activation in the left ventricle of the heart, and this stimulates cardiomyocyte hypertrophy in a Gαs-dependent manner.
Authors:
Kimberley C W Wang; Doug A Brooks; Kent L Thornburg; Janna L Morrison
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-28
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-02     Completed Date:  2013-03-25     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  5425-37     Citation Subset:  IM    
Affiliation:
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide, SA, Australia 5001.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Coronary Vessels
Cyclic AMP-Dependent Protein Kinases / physiology
Fetus
Gestational Age
Heart Ventricles / pathology*
Hypertrophy
Insulin-Like Growth Factor II / pharmacology
Myocytes, Cardiac / pathology*
Receptor, IGF Type 2 / physiology*
Sheep
Chemical
Reg. No./Substance:
0/Receptor, IGF Type 2; 67763-97-7/Insulin-Like Growth Factor II; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases
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