PhD ceremony Ms. M.E. Smilde-Baardman: Understanding the origin of congenital heart disease. Is there a role for maternal cholesterol in cardiac development?
|When:||We 05-02-2014 at 14:30|
|Where:||Academiegebouw, Broerstraat 5, Groningen|
PhD ceremony: Ms. M.E. Smilde-Baardman
Dissertation: Understanding the origin of congenital heart disease. Is there a role for maternal cholesterol in cardiac development?
Promotor(s): prof. R.M.W. Hofstra, prof. R.M.F. Berger
Faculty: Medical Sciences
Congenital heart disease (CHD) affects approximately 1 in 150 pregnancies in the Netherlands. It is a major cause of neonatal death and it often has a great impact on the life of survivors. In the research presented in this thesis, both genetic and environmental risk factors for CHD were explored in order to gain a better understanding of the origin of CHD, with a special focus on the role of maternal cholesterol. This thesis provides evidence that maternal life style factors - smoking and high body mass index - interact in the risk they convey for CHD in offspring, implying they share a biological mechanism in the development of CHD. Furthermore, insight has been gained into the contribution of maternal cholesterol, which is transported to the foetus during pregnancy, and in the foetus's own cholesterol synthesis. We have identified two new key players involved in the genetics of cardiac development, namely lipoprotein-related receptor protein 2 (LRP2) and Smoothened (SMO). Both genes are related to the SHH-pathway, a pathway that depends on sufficient cholesterol levels. Our studies support the hypothesis that CHD is a complex disorder, caused by an interaction between genetic and environmental factors. Future research should focus on maternal cholesterol as a possible modifier in foetal cardiac development.