Thesis defense Anne de Leeuw ‘Decoding heavy hearts: Molecular insights into Hypertrophic Cardiomyopathy’

Hypertrophic Cardiomyopathy (HCM) is a complex condition which affects the heart muscle. The condition can be caused by a single mutationAn error in the DNA. Mutations can, among other things, arise if the DNA is copied incorrectly or through external influences. For example, tumor cells often contain mutations that are beneficial for their growth. and is classified as the most prevalent genetic heart disease affecting roughly 1 in 500 to 1 in 200 people in the western world. Many of these people will not develop any symptoms of the condition. However, some patients develop very severe symptoms which can even require a heart transplant. Despite the prevalence of the disease, there is still a lack of information about how the disease begins and progresses and what the exact genetic cause for symptom development is.

Patients have a heavy heart

The condition is primarily characterized by the thickening of the heart muscle, a process also called remodeling. This results in patients having a heavy heart. The thickening of the heart usually happens through the enlargement of heart cells located between our two ventricles, an area called the septum. During her PhD, de Leeuw used human heart cells, also called cardiomyocytes, to investigate what genes are involved in the onset of cell remodeling. She used the heart cells to study the difference between healthy and diseased cells and was able identify a common protein which was present in diseased cells. This enabled her to make predictions about which genes were involved in the cell remodeling.

Some heart cells are more prone to thickening

De Leeuw next investigated why the thickening is more commonly seen in the heart septum compared to other areas of the heart. She used Tomo-sequencing, which is a technique used to study the gene expressionThe activity of a gene or genes. The combination of active genes in a cell determines, amongst other things, the function, shape and size of the cell. of the septum cells. This enabled her to identify a protein which influenced the onset of the remodeling process. The identification of the protein markers for diseased cells and the prediction of the genes involved in heart cell thickening can be used to uncover the molecular mechanisms behind HCM development. The results of De Leeuw’s project can ultimately help develop better treatment strategies for patients with HCM.