PhD defence J. (Jens) van de Wouw

In the first part of this thesis, we show that diabetes and high cholesterol can lead to changes in the small blood vessels in various organs, resulting in cardiovascular disease. In addition, we showed how diabetes and high cholesterol affect the function of the heart muscle with changes in gene expression and protein expression, while the structure of the heart was unaffected. We have shown that this impaired the relaxation of the heart. Additionally, we showed that these risk factors did not directly result in an increase in von Willebrand factor while factor VIII did increase.

In part 2 of this thesis, we showed that the addition of chronic kidney disease resulted in the same functional changes as in part 1. Furthermore, we also observed structural changes of the heart, resulting in reduced relaxation. In addition to the disturbed relaxation of the heart, we also showed that the risk factors resulted in a disturbed oxygen balance in the heart, which resulted in a relative oxygen deficiency in the heart. We went on to show that the functional changes in the small blood vessels in the heart were due to a decreased relaxation of the small blood vessels due to reduced bioavailability of nitric oxide. Finally, we investigated how the combined risk factors also affect the pulmonary vessels, resulting in increased vascular resistance in the pulmonary arteries. Surprisingly, this was not due to a change in nitric oxide availability but due to increased endothelin 1, a protein that causes vasoconstriction.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall of the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.