Akt signaling as a mediator of cardiac adaptation to low birth weight

Kimberley Wang, Kimberley J. Botting, Song Zhang, Caroline McMillen, Doug Brooks, Janna Morrison

Research output: Contribution to journalReview article

6 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)R81–R94
JournalThe Journal of Endocrinology
Volume233
Issue number2
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

Fingerprint

Low Birth Weight Infant
MicroRNAs
Cardiac Myocytes
Cardiovascular Diseases
Placental Insufficiency
IGF Type 2 Receptor
IGF Type 1 Receptor
Insulin-Like Growth Factor II
Health
Angiotensins
Left Ventricular Hypertrophy
DNA Methylation
Acetylation
Insulin-Like Growth Factor I
Histones
Epidemiologic Studies
Phosphorylation
Apoptosis
Phenotype
Gene Expression

Cite this

Wang, Kimberley ; Botting, Kimberley J. ; Zhang, Song ; McMillen, Caroline ; Brooks, Doug ; Morrison, Janna. / Akt signaling as a mediator of cardiac adaptation to low birth weight. In: The Journal of Endocrinology. 2017 ; Vol. 233, No. 2. pp. R81–R94.
@article{caac8943f7ad413cbf43954728188582,
title = "Akt signaling as a mediator of cardiac adaptation to low birth weight",
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.",
author = "Kimberley Wang and Botting, {Kimberley J.} and Song Zhang and Caroline McMillen and Doug Brooks and Janna Morrison",
year = "2017",
month = "5",
day = "1",
doi = "10.1530/JOE-17-0039",
language = "English",
volume = "233",
pages = "R81–R94",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "BioScientifica Ltd",
number = "2",

}

Akt signaling as a mediator of cardiac adaptation to low birth weight. / Wang, Kimberley; Botting, Kimberley J.; Zhang, Song; McMillen, Caroline; Brooks, Doug; Morrison, Janna.

In: The Journal of Endocrinology, Vol. 233, No. 2, 01.05.2017, p. R81–R94.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Akt signaling as a mediator of cardiac adaptation to low birth weight

AU - Wang, Kimberley

AU - Botting, Kimberley J.

AU - Zhang, Song

AU - McMillen, Caroline

AU - Brooks, Doug

AU - Morrison, Janna

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

U2 - 10.1530/JOE-17-0039

DO - 10.1530/JOE-17-0039

M3 - Review article

VL - 233

SP - R81–R94

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 2

ER -