Akt signaling as a mediator of cardiac adaptation to low birth weight
Date
2017
Authors
Wang, K.
Botting, K.
Zhang, S.
McMillen, C.
Brooks, D.
Morrison, J.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Endocrinology, 2017; 233(2):R81-R94
Statement of Responsibility
Kimberley C W Wang, Kimberley J Botting, Song Zhang, I Caroline McMillen, Doug A Brooks and Janna L Morrison
Conference Name
Abstract
Intrauterine insults, such as poor nutrition and placental insufficiency, can alter cardiomyocyte development, and this can have significant long-term implications for heart health. Consequently, epidemiological studies have shown that low-birth-weight babies have an increased risk of death from cardiovascular disease in adult life. In addition, intrauterine growth restriction can result in increased left ventricular hypertrophy, which is the strongest predictor for poor health outcomes in cardiac patients. The mechanisms responsible for these associations are not clear, but a suboptimal intrauterine environment can program alternative expression of genes such as cardiac IGF-2/H19, IGF-2R and AT1R through either an increase or decrease in DNA methylation or histone acetylation at specific loci. Furthermore, hypoxia and other intrauterine insults can also activate the IGF-1 receptor via IGF-1 and IGF-2, and the AT1 receptor via angiotensin signaling pathways; both of which can result in the phosphorylation of Akt and the activation of a range of downstream pathways. In turn, Akt activation can increase cardiac angiogenesis and cardiomyocyte apoptosis and promote a reversion of metabolism in postnatal life to a fetal phenotype, which involves increased reliance on glucose. Cardiac Akt can also be indirectly regulated by microRNAs and conversely can target microRNAs that will eventually affect other specific cardiac genes and proteins. This review aims to discuss our understanding of this complex network of interactions, which may help explain the link between low birth weight and the increased risk of cardiovascular disease in adult life.
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Dissertation Note
Provenance
Description
This article is adapted from work presented at the Aspen/Snowmass Perinatal Biology Symposium, 27–30 August 2016. The meeting was supported in part by the Journal of Endocrinology.
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© 2017 Society for Endocrinology. Published by Bioscientifica Ltd.