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PMID: 21807611 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

The Journal of physiology ·Vol. 589 ·No. Pt 19 ·2011-10-01 ·Pages 4709-22

Wang KC, Zhang L, McMillen IC, Botting KJ, Duffield JA, Zhang S, Suter CM, Brooks DA, Morrison JL

Abstract

Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

MeSH Terms
Animals Cardiomegaly/genetics,metabolism DNA Methylation Fetal Growth Retardation/genetics,metabolism Fetus/embryology,metabolism Gene Expression/genetics Heart/embryology,growth & development Heart Ventricles/embryology,growth & development,metabolism Insulin-Like Growth Factor I/genetics,metabolism Insulin-Like Growth Factor II/biosynthesis,genetics,metabolism Myocardium/metabolism Myocytes, Cardiac/metabolism RNA, Messenger/genetics,metabolism Receptor, IGF Type 1/genetics,metabolism Receptor, IGF Type 2/genetics,metabolism Sheep Signal Transduction
Chemicals
RNA, Messenger Receptor, IGF Type 2 Insulin-Like Growth Factor I Insulin-Like Growth Factor II Receptor, IGF Type 1
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wang Kimberley C W
Heart Foundation and NHMRC Career Development Research Fellow, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5001, Australia. [email protected]
Zhang Lei
McMillen I Caroline
Botting Kimberley J
Duffield Jaime A
Zhang Song
Suter Catherine M
Brooks Doug A
Morrison Janna L
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
1469-7793
DOI
10.1113/jphysiol.2011.211185
Email
[email protected]
Published
2011-10-01
Epub
2011-00-01
Pages
4709-22
Language
English
Region
England
NLM ID
0266262
PMCID
PMC3213418
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.2011.211185 PMC Full Text View journal details
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