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Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.
J Physiol. 2011 Oct 01; 589(Pt 19):4709-22.JP

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.

Authors+Show Affiliations

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. janna.morrison@unisa.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21807611

Citation

Wang, Kimberley C W., et al. "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, pp. 4709-22.
Wang KC, Zhang L, McMillen IC, et al. Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb. J Physiol. 2011;589(Pt 19):4709-22.
Wang, K. C., Zhang, L., McMillen, I. C., Botting, K. J., Duffield, J. A., Zhang, S., Suter, C. M., Brooks, D. A., & Morrison, J. L. (2011). Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb. The Journal of Physiology, 589(Pt 19), 4709-22. https://doi.org/10.1113/jphysiol.2011.211185
Wang KC, et al. Fetal Growth Restriction and the Programming of Heart Growth and Cardiac Insulin-like Growth Factor 2 Expression in the Lamb. J Physiol. 2011 Oct 1;589(Pt 19):4709-22. PubMed PMID: 21807611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb. AU - Wang,Kimberley C W, AU - Zhang,Lei, AU - McMillen,I Caroline, AU - Botting,Kimberley J, AU - Duffield,Jaime A, AU - Zhang,Song, AU - Suter,Catherine M, AU - Brooks,Doug A, AU - Morrison,Janna L, Y1 - 2011/08/01/ PY - 2011/8/3/entrez PY - 2011/8/3/pubmed PY - 2012/5/29/medline SP - 4709 EP - 22 JF - The Journal of physiology JO - J Physiol VL - 589 IS - Pt 19 N2 - 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. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/21807611/Fetal_growth_restriction_and_the_programming_of_heart_growth_and_cardiac_insulin_like_growth_factor_2_expression_in_the_lamb_ L2 - https://doi.org/10.1113/jphysiol.2011.211185 DB - PRIME DP - Unbound Medicine ER -