Supervisor: Dino Guissani
Developmental Programming of Heart Disease: Towards Intervention
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 the risk of heart disease in adult life (1,2). However, the mechanisms underlying this developmental programming of cardiovascular disease in complicated pregnancy remain unknown. Recently, we have shown in animal models that chronic fetal hypoxia, one of the most common consequences of complicated pregnancy, induces oxidative stress in the fetal heart and circulation and programmes cardiometabolic dysfunction at adulthood. Furthermore, maternal treatment with the antioxidant vitamin C in hypoxic pregnancy prevented these effects (1). While this discovery implicates developmental oxidative stress as a causative mechanism and thereby potential targets for intervention, only high doses of vitamin C incompatible with human treatment, were effective. Therefore, there is an urgent need to identify alternative therapies, compatible with human treatment, for clinical translation. The focus of our laboratory is now on addressing the role of mitochondria-targeted antioxidants and of gasotransmitters, such as carbon monoxide and hydrogen sulphide, as effective human clinical translational therapy. During a PhD, students are encouraged to address a focussed question at several levels, combining in vivo experiments with those at the isolated organ, cellular, molecular and epigenetic levels. This approach not only increases the depth of investigation and thereby impact of publication, but also ensures broad training in research skills, including highly vulnerable expertise in cardiovascular function.
http://news.sciencemag.org/sciencenow/2012/02/embryos-starved-of-oxygen-may-be.html
1. Giussani DA, Davidge ST. J Dev Orig Health Dis. 2013; 4(5):328-37. Review.
2. Allison et al. FASEB J. 2016; 30(5):1968-75.
3. Niu et al. Hypertension. 2018 Oct; 72(4):971-978