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: Kimberley C W Wang, Doug A Brooks, Kent L Thornburg, Janna L Morrison
• Journal: The Journal of physiology (J Physiol) Vol. 590 Issue 21 Pg. 5425-37 (Nov 01 2012) ISSN: 1469-7793 [Electronic] England
• PMID: 22930271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, IGF Type 2
• Insulin-Like Growth Factor II
• Cyclic AMP-Dependent Protein Kinases

Topics

• 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