Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus

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dc.contributor.authorWang, K.
dc.contributor.authorBrooks, D.
dc.contributor.authorThornburg, K.
dc.contributor.authorMorrison, J.
dc.date.issued2012
dc.description.abstractIn 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.
dc.description.statementofresponsibilityKimberley C.W.Wang, Doug A. Brooks, Kent L. Thornburg, and Janna L. Morrison
dc.identifier.citationJournal of Physiology, 2012; 590(21):5425-5437
dc.identifier.doi10.1113/jphysiol.2012.238410
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.orcidBrooks, D. [0000-0001-9098-3626]
dc.identifier.urihttp://hdl.handle.net/2440/96515
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/349405
dc.rights© 2012 The Authors
dc.source.urihttps://doi.org/10.1113/jphysiol.2012.238410
dc.subjectCoronary Vessels
dc.titleActivation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus
dc.typeJournal article
pubs.publication-statusPublished

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