Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons

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.

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

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

“…Recent studies suggest that overall heart function declines with ageing in the baboon (Kuo et al . a , b ), but no studies have reported normative declines across the life course.…”

Section: Introductionmentioning

confidence: 99%

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.)

Kuo

Huber

et al. 2018

Self Cite

Previous studies reported cardiac function declines with ageing. This study determined changes in biventricular cardiac function in a well-characterized baboon model. Cardiac magnetic resonance imaging measured key biventricular parameters in 47 baboons (22 female, age 4-23 years). ANCOVA assessed sex and age changes with P < 0.05 deemed significant. Stroke volume, cardiac output and other cardiac functional parameters were normalized to body surface area. There were similar, age-related rates of decrease in male (M) and female (F) normalized left ventricular (LV) myocardial mass index (M: -1.2 g m year , F: -0.9 g m year ). LV ejection fraction declined at -0.96% year (r = -0.43, P = 0.002) and right ventricular (RV) ejection fraction decreased at -1.2% year (r = -0.58, P < 0.001). Normalized LV stroke volume fell at -1.1 ml m year (r = -0.47, P = 0.001), normalized LV ejection rate at -3.8 ml s m year (r = -0.43, P < 0.005) and normalized LV filling rate at -4.1 ml s m year (r = -0.44, P < 0.005). Also, RV wall thickening fraction decreased with age (slope = -1% year , P = 0.008). RV ejection rate decreased at -3.6 ml s m year (P = 0.002) and the normalized average RV filling rate dropped at -3.7 ml s m year (P < 0.0001). End-systolic RV sphericity index also dropped with age (r = -0.33, P = 0.02). Many observed changes parallel previously reported data in human and animal studies. These measured biventricular functional declines in hearts with ageing from the closest experimental primate species to man underscore the utility of the baboon model for investigating mechanisms related to heart ageing.

“…In line with observations in human IUGR offspring, there are now elegant non‐human primate data derived from cardiac magnetic resonance imaging that reports IUGR also being associated with cardiac remodelling in young adult baboons (Kuo et al . ,b). Studies in rodent mammalian animal models have also reported that chronic fetal hypoxia can programme cardiac and vascular dysfunction in later life (Thompson & Weiner, ; Kim et al .…”

Section: Introductionmentioning

confidence: 99%

The highs and lows of programmed cardiovascular disease by developmental hypoxia: studies in the chicken embryo

Itani

Salinas

Villena

et al. 2017

It is now established that adverse conditions during pregnancy can trigger a fetal origin of cardiovascular dysfunction and/or increase the risk of heart disease in later life. Suboptimal environmental conditions during early life that may promote the development of cardiovascular dysfunction in the offspring include alterations in fetal oxygenation and nutrition as well as fetal exposure to stress hormones, such as glucocorticoids. There has been growing interest in identifying the partial contributions of each of these stressors to programming of cardiovascular dysfunction. However, in humans and in many animal models this is difficult, as the challenges cannot be disentangled. By using the chicken embryo as an animal model, science has been able to circumvent a number of problems. In contrast to mammals, in the chicken embryo the effects on the developing cardiovascular system of changes in oxygenation, nutrition or stress hormones can be isolated and determined directly, independent of changes in the maternal or placental physiology. In this review, we summarise studies that have exploited the chicken embryo model to determine the effects on prenatal growth, cardiovascular development and pituitary-adrenal function of isolated chronic developmental hypoxia.