Early origins of heart disease: Low birth weight and the role of the insulin‐like growth factor system in cardiac hypertrophy

Wang, Kimberley C. W.; Botting, Kimberley J.; Padhee, Monalisa; Zhang, Song; McMillen, I. C.; Suter, Catherine M.; Brooks, Doug A.; Morrison, Janna L.

doi:10.1111/j.1440-1681.2012.05743.x

Cited by 22 publications

(22 citation statements)

References 115 publications

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“…; Wang et al . ). Suboptimal intrauterine conditions can result in epigenetic changes to the IGF2/H19 and IGF2R genes (Li et al .…”

Section: Discussionmentioning

confidence: 97%

“…Linear regression was used to determine the relationship between mean fetal gestational plasma glucose as well as mean arterial blood pressure with mRNA and protein expression (GraphPad Prism version 7.03 for Windows, GraphPad Software, La Jolla, CA, USA). All genes and proteins studied were selected a priori based on their known biological role in cardiac development, growth and previously identified roles in the fetal heart (Morrison et al 2007;Wang et al 2011Wang et al , 2012aWang et al , 2012bBotting et al 2012).…”

Section: Statistical Analysesmentioning

confidence: 99%

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Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart

Darby

McMillen

Morrison

2018

The Journal of Physiology

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Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life.

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“…; Wang et al . ). Suboptimal intrauterine conditions can result in epigenetic changes to the IGF2/H19 and IGF2R genes (Li et al .…”

Section: Discussionmentioning

confidence: 97%

Section: Statistical Analysesmentioning

confidence: 99%

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart

Darby

McMillen

Morrison

2018

The Journal of Physiology

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“…; Wang et al . , ). Although IGF1 mRNA expression was increased in the RSV‐treated group, there was no evidence that downstream AKT/mTOR signalling was increased.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Darby

Saini

Soo

et al. 2019

The Journal of Physiology

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Key points Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight. RSV was not detectable in the fetal circulation, indicating that it may not cross the sheep placenta. This study highlights RSV as a possible intervention to restore fetal substrate supply in pregnancies affected by placental insufficiency. Abstract Suboptimal in utero environments with reduced substrate supply during critical developmental windows of gestation predispose offspring to non‐communicable diseases such as cardiovascular disease (CVD). Improving fetal substrate supply in these pregnancies may ameliorate the predisposition these offspring have toward adult‐onset CVD. This study aimed to determine the effect of maternal resveratrol (RSV) supplementation on uterine artery blood flow and the direct effects of RSV on the fetal heart in a chronically catheterised sheep model of human pregnancy. Maternal RSV treatment significantly increased uterine artery blood flow as measured by phase contrast magnetic resonance imaging, mean gestational fetal PnormalaO2 and SnormalaO2 as well as fetal weight. RSV was not detectable in the fetal circulation, and mRNA and protein expression of the histone/protein deacetylase SIRT1 did not differ between treatment groups. No effect of maternal RSV supplementation on AKT/mTOR or CAMKII signalling in the fetal left ventricle was observed. Maternal RSV supplementation is capable of increasing fetal oxygenation and growth in an animal model in which cardiac development parallels that of the human.

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“…nutrition, extracellular growth factors, mechanical stress, ECM 51-54 ) and/or ligand-receptors interactions (e.g. thyroid hormone 43 , insulin-like receptors 55,56 , adrenergic receptors 57 , etc.) as previously identified in cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development

López

Sharma

Ávila

et al. 2017

Journal of Molecular and Cellular Cardiology

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Rationale Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue. Objective To develop a new MC-specific large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs. This approach is developed to enable growth-scaled measurements per-cell of the MC proteome and sarcomeric protein (i.e. myosin heavy chain (MyHC) and alpha-actin (α-actin)) content. Methods and Results Individual cardiac cells were isolated from 21-94 days old mice. An LP-FACS jet-in-air system with a 200-μm nozzle was defined by the first time to purify adult MCs. Cell-type specific immunophenotyping and sorting yielded ≥95% purity of adult MCs independently of cell morphology and size. This approach excluded other cell types and tissue contaminants from further analysis. MC proteome, MyHC and α-actin proteins were measured in linear biochemical assays normalized to cell numbers. Using the allometric coefficient α, we scaled the MC-specific rate of protein accumulation to growth post-weaning. MC-specific volumes (α=1.02) and global protein accumulation (α=0.94) were proportional (i.e. isometric) to body mass. In contrast, MyHC and α-actin accumulated at a much greater rate (i.e. hyperallometric) than body mass (α= 1.79 and 2.19 respectively) and MC volumes (α= 1.76 and 1.45 respectively). Conclusion Changes in MC proteome and cell volumes measured in LP-FACS purified MCs are proportional to body mass post-weaning. Oppositely, MyHC and α-actin are concentrated more rapidly than what would be expected from MC proteome accumulation, cell enlargement, or animal growth alone. LP-FACS provides a new standard for adult MC purification and an approach to scale the biochemical content of specific proteins or group of proteins per cell in enlarging MCs.

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Early origins of heart disease: Low birth weight and the role of the insulin‐like growth factor system in cardiac hypertrophy

Cited by 22 publications

References 115 publications

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth

Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development

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