Together with her Rotterdam colleague, cardiologist Peter-Paul Zwetsloot, she has been awarded the Dekker Grant from the Dutch Heart Foundation for this research.
Hereditary heart muscle diseases can cause serious damage at a young age, resulting in heart failure, cardiac arrhythmia, or even sudden death. In the Netherlands, thousands of people carry DNA abnormalities in genes such as DES and MYH7. These have often been present in families for generations. Vermeer: "Yet the disease progresses differently in each carrier. One person may develop a thickened heart, while another may develop a weakened or stiff heart muscle. This makes it difficult to identify at an early stage who is at risk and which treatment is most appropriate. In addition, people often only visit a cardiologist when symptoms are already present, which means that early changes in the heart muscle remain invisible."
To break this cycle, Vermeer and Zwetsloot are developing a way to more accurately mimic hereditary heart disease in the laboratory. This part of their research is being conducted at the UMCG. Vermeer: ‘We have already applied the method used in this research in the lab. The genetic variants that occur in heart muscle tissue have already been mapped. And the method for creating a specific stem cell that is needed for our research has also proven successful. So we can really kick-start our study."
They use one type of stem cell for their research. Using modern techniques, they introduce a different DNA abnormality into each cell that also occurs in patients. The different stem cells first grow into heart muscle cells, after which the researchers create small pieces of ‘mini heart muscle’ from each variant. In these mini heart muscles, the disease process becomes visible step by step, from the first subtle signs to later, more serious changes. Because all mini heart muscles come from the same type of stem cell and only the DNA abnormality differs, the researchers can see exactly what effect each abnormality has.
In addition, the researchers collect medical data and material from Dutch patients with these DNA abnormalities. These are stored in the Dutch Cardiovascular Database. Vermeer: 'We link this information to the findings from the laboratory. This allows us to better understand why hereditary abnormalities are mild in one person and much more severe in another.'
This research shows what goes wrong in the heart muscle under which circumstances in the case of hereditary DNA abnormalities. ‘Our goal is to identify biomarkers that indicate that someone is going to become ill,’ says Vermeer. 'This knowledge helps to better inform carriers about their risk and to monitor them more closely.' The mini heart muscle models also offer a safe way to test drugs that can intervene at an early stage. 'This will enable us to contribute to the earlier detection and better, more personalized treatment of people with hereditary heart muscle diseases.'
This Dekker Grant of €650,000 is intended for a duo consisting of a physician and a more fundamental researcher from different research centers. With this grant, the Dutch Heart Foundation enables researchers to engage in long-term scientific research into cardiovascular disease. The grant is named after Dr. E. Dekker, former director of the Heart Foundation. He was the initiator of citizen assistance in the event of cardiac arrest in the Netherlands.
