Fetal hypoxia and developmental programming of heart disease.
The interaction between genetic make-up and environmental risk factors, such as smoking and obesity, promote a risk of heart disease. In addition, the concept of developmental programming has now become established. This states that a component of heart health and disease can be programmed before birth by the quality of the prenatal environment. The most common feature of complicated pregnancy, such as during preeclampsia or placental insufficiency, is fetal hypoxia. Over last 7 years, working under the supervision from Prof. Giussani, I have shown, in a variety of species, including chicken, rat, and sheep, that prental hypoxia programmes caridiac dysfunction at both fetal and adulthood stage, and this programming process is secondary to oxidative stress. Therefore, I have been testing different antioxidant strategies to prevent the developmental programming of heart disease by chronic fetal hypoxia. The significance of my work has been well recognised by receiving two Pfizer President’s Presenter’s Awards, and one Best New Investigator Poster Award at Annual Scientific Meeting for the Society of Reproductive Investigation (SRI).
Perinatal glucocorticoid treatment and developmental programming of heart disease.
In fetal development, a prepartum surge in glucocorticoids is necessary to prepare the fetus for the transition from intrauterine life to extrauterine life. This prepartum surge has many maturational effects upon several organ systems in the fetus, including the lungs, liver, kidneys and gut. In particular, the maturation of the fetal lungs is highly glucocorticoid dependent. Therefore, glucocorticoid treatment has been widely used to treat or prevent chronic lung disease (CLD) in premature infants. However, in addition to the beneficial effects of glucocorticoids on lung maturation, they have also been shown to have adverse side-effects on cardiovascular function. I have shown that postnatal treatment with synthetic glucocorticoid, dexamethasone, programmes cardiac dysfunction at adulthood and this detrimental effect is prevented by combined antioxidant treatment of vitamins C and E. This work has been published in Journal of Physiology. Now, working on Prof. Giussani’s Programme Project funded by the British Heart Foundation, I am investigating whether combining chronic fetal hypoxia with antenatal glucocorticoid treatment will programme heart disease in later life, and working on the potential intervention stragety.
Cardiac metabolism and developmental programming of heart disease.
Since cardiac metabolism is critically linked to cardiac function, I have begun to think about whether there is a link between cardiac metabolism and developmental programming of heart disease. To investigate this will integrate my experience and expertise in determining cardiac function and cardiac metabolism with an established rodent model of developmental programming of heart disease by prenatal hypoxia.
Thakor AS, Allison BJ, Niu Y, Botting KJ, Serón-Ferré M, Herrera EA, Giussani DA, (2015), Melatonin modulates the fetal cardiovascular defense response to acute hypoxia, J Pineal Res, Aug;59(1):80-90. doi: 10.1111/jpi.12242. Epub 2015 May 13
Blackmore HL, Niu Y, Fernandez-Twinn DS, Tarry-Adkins JL, Giussani DA, Ozanne SE, (2014), Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight, Endocrinology, 155(10): 3970-3980
Niu Y, Herrera EA, Evans RD, Giussani DA, (2013), Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy, J Physiol, 591(20): 5083-5093 [Epub ahead of print]
Cindrova-Davies T, Herrera EA, Niu Y, Kindom J, Giussani DA, Burton GJ, (2013), Reduced cystathionine γ-lyase and increased miR-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: hydrogen sulfide as a placental vasodilator, AM J Pathol, 182(4):1448-58
Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, Blake EZ, Horder KA, Thakor AS, Hansell JA, Kane AD, Wooding FB, Cross CM, Herrera EA, (2012), Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress, PLoS One, 7(2): e31017
Herrera EA, Kane AD, Hansell JA, Thakor AS, Allison BJ, Niu Y, Giussani DA, (2012), A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep, J Physiol, 590(pt8):1825-37
Wood NI, Sawiak SJ, Buonincontri G, Niu Y, Kane AD, Carpenter TA, Giussani DA, Morton AJ, (2012), Direct evidence of progressive cardiac dysfunction in a transgenic mouse model of Huntington’s disease, Journal of Huntington’s Disease, 1 57-54
Niu Y, Evans RD, (2011), Very-low-density-lipoprotein: complex particles in cardiac energy metabolism, Journal of Lipids, 189876, Epub 2011 July 3
Niu Y, Evans RD, (2009), Myocardial metabolism of triacylglycerol-rich lipoproteins in type 2 diabetes, Journal of Physiology, Jul 1;587(Pt 13):3301-15, Epub 2009 May 11
Niu Y, Evans RD, (2008), Metabolism of triacylglycerol-rich lipoproteins by the streptozotocin-treated rat hearts: effects of diabetes and lipoprotein preferences, American Journal of Physiology-Endocrinology and Metabolism, Nov;295(5):E1106-16, Epub 2008 Sep 9
Niu Y, Hauton D, Evans RD, (2004), Utilisation of triacylglycerol-rich lipoproteins by the working rat hearts: routes of uptake and metabolic fate, Journal of Physiology, 558.1:225-237
Evans RD, Niu Y, (2008), Hypolipidaemic effects of high-dose insulin therapy, British Journal of Anaesthesia, Apr;100(4):429-33