On Tuesday 16 June 2020, J. Burger will defend her PhD dissertation, entitled: ‘Molecular Mechanisms of Aortic Aneurysms’.
Cardiovascular diseases are one of the leading causes of mortality. They include aortic diseases such as aortic aneurysms, dilatations of the aorta that result in thinning of the aortic wall which eventually leads to aortic dissections or rupture of the aorta. Currently the only treatments are surgical repair of the aneurysm by placement of a stent. A better understanding of the molecular mechanisms and causative genes is needed for better diagnosis of aneurysm patients as well as to develop new treatments.
We developed functional tests that could identify the pathogenicity of variants found in aneurysm patients. As a prove of principle we started with mutations that were proven to be pathogenic and caused aneurysms in patients. We found that we could distinguish patients cells with pathogenic mutations from control cells based on the skeleton these cells made as well as their contractility and migration. With these tests and baseline outcomes we can start to test patients cells of which the effect is unknown which can result in a better diagnosis.
Additionally, we investigated vascular smooth muscle cells (VSMCs) of different mouse models that develop aneurysm to better understand why these mice develop aneurysms. We found alterations in the cytoskeleton of VSMCs, in their extracellular matrix as well as in their mitochondria. The mitochondrial alterations were also found in aortic tissue of patients with aneurysms.
Our findings show novel pathways that are involved in aortic aneurysm formation are still being identified and could be useful for development of treatments.
The PhD defences will not take place publicly in the Senate Hall or Professor Andries Queridoroom due to the coronavirus. The candidates will defend their thesis online.