title: Activation of IGF-2R stimulates cardiomyocyte hypertrophy in the late gestation sheep fetus.
abstract: 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.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.
authors.forename: Kimberley C W
authors.initials: KC
authors.lastname: Wang
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005333:Fetus; D005865:Gestational Age; D006352:Heart Ventricles / Q000473:pathology*; D006984:Hypertrophy; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000473:pathology*; D017527:Receptor, IGF Type 2 / Q000502:physiology*; D012756:Sheep
chemical_list: D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D017868:Cyclic AMP-Dependent Protein Kinases