DEVELOPMENTAL PROGRAMMING OF HEART HEALTH.
In addition to genetics and lifestyle risk factors, it is now accepted that the quality of the intrauterine environment also plays a role in shaping cardiovascular function in adult life. In turn, the quality of the intrauterine environment is primarily determined by the available nutrient and oxygen supply to the unborn child. Consequently, several studies have reported that reductions in oxygen and nutrient delivery to the fetus, as occurs in placental insufficiency or preeclampsia, can trigger cardiovascular abnormalities in the adult offspring. However, the mechanisms underlying developmental programming of alterations in cardiovascular health in offspring from complicated pregnancy remain unknown. This PhD project will test the hypothesis that oxidative stress underlies the molecular basis via which developmental programming of alterations in cardiovascular health occur in offspring from complicated pregnancy. If true, maternal treatment with antioxidants of complicated pregnancies may offer plausible clinical intervention to maintain cardiovascular health in the offspring. Using an integrative approach at the whole animal, isolated organ, cellular and molecular level, we have shown in several animal models that prenatal hypoxia promotes aortic and cardiac wall thickening with endothelial and cardiac dysfunction in the adult offspring. Further, these effects can be prevented by maternal treatment with vitamin C. While this provides proof of concept, only extremely high doses of vitamin C proved effective, making translation to human difficult. The PhD will adopt a similar approach to test different antioxidant regimes. http://news.sciencemag.org/sciencenow/2012/02/embryos-starved-of-oxygen-may-be.html
- Giussani, D.A., Camm, E.J., Niu, Y., Richter, H.G., Blanco, C.E., Gottschalk, R., Blake, E.Z., Horder, K.A., Thakor, A.S., Hansell, J.A., Kane, A.D., Wooding, F.B.P., Cross C.M. & Herrera. E.A. (2012). Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS ONE 7(2): e31017.
- News piece written in Science Magazine about this work entitled: Embryos Starved of Oxygen May Be 'Programmed' for Heart Disease by Jean Friedman-Rudovsky on 13 February 2012. http://news.sciencemag.org/sciencenow/2012/02/embryos-starved-of-oxygen-may-be.html
- Richter, H.G., Camm, E.J., Modi, B.N., Naeem, F., Cross, C.M., Cindrova-Davies, T., Spasic-Boskovic, O., Dunster, C., Mudway, I.A., Kelly, F.J., Burton, G.J., Poston, L. & Giussani, D.A. (2012). Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats. Journal of Physiology 590.6, 1377-1387. Paper selected as Editor's Choice.
- Niu, Y., Herrera, E.A., Evans, R.D. & Giussani, D.A. (2013). Antioxidant treatment improves postnatal survival and prevents impaired cardiac function in at adulthood following postnatal glucocorticoid therapy. J. Physiol. 591(Pt 20), 5083-93. Paper selected for Editorial Perspectives.