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 AT1receptor 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.
authors.affiliation: Early Origins of Adult Health Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Kimberley C W
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Early Origins of Adult Health Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Kimberley J
authors.initials: KJ
authors.lastname: Botting
authors.affiliation: Early Origins of Adult Health Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Early Origins of Adult Health Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
authors.affiliation: Mechanisms in Cell Biology and Disease Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Doug A
authors.initials: DA
authors.lastname: Brooks
authors.affiliation: Early Origins of Adult Health Research GroupSchool of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia Janna.Morrison@unisa.edu.au.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; IGFs; cardiac hypertrophy; epigenetics; intrauterine growth restriction