In 2024, researcher Renee Maas received the very first heart tissue made available by the Heart Bank. She is using this heart tissue for her research into the genetic heart muscle disorder PLN-R14del. We spoke to her about her research.

Renee Maas is a biomedical researcher at UMC Utrecht and conducts research into hereditary heart diseases. On 13 March, she obtained her PhD on the subject of ‘Potentials of stem cell-derived cardiomyocytes: From disease modelling to therapeutic strategies’. She researched diseases of the heart muscle, which are often caused by a defect in the DNA. One consequence of this is that the heart cannot pump blood through the body properly.

What is PLN?

PLN (phospholamban) is a crucial protein for calcium regulation and thus the contraction of the heart muscle. A specific DNA error (R14del mutation) was only recently discovered in 2010. In people with the PLN-R14del mutation, the PLN protein does not function properly because part of the genetic code needed to produce this protein is missing. Renee explains: ‘As a result, misfolded PLN-R14del protein accumulates in the heart muscle cells and these cells die. A dead heart muscle cell is not replaced and cannot repair itself, causing the heart to eventually lose its pumping power, also known as heart failure.’ The effect of the PLN-R14del mutation varies from person to person: fat or connective tissue replaces the heart muscle, the heart muscle can dilate and, in the most extreme cases, it can even lead to cardiac arrest. Ultimately, everyone with this mutation will suffer from heart failure, although the timing varies.

What is your research about?

“My new research focuses on what exactly goes wrong with PLN-R14del. What exactly do the heart cells of people with PLN-R14del do? We want to map out how many protein processes are already disrupted in people who do not yet suffer from PLN-related symptoms. We are also looking at which factors play a role in this. This will enable us to determine at what age and at what point (before symptoms appear or only when symptoms start) we should start treating someone with PLN-R14del. Ultimately, I will compare the tissue of people who do not yet have any symptoms with that of people who already do have symptoms.”

Why PLN?

During my second internship, my supervisors Alain van Mil and Joost Sluijter at UMC Utrecht assigned me a project to create heart muscle cells using stem cells. These stem cells can be reprogrammed from skin biopsies or blood. Shortly afterwards, I met Pieter Glijnis, a patient with PLN and founder of the PLN Foundation. I used his stem cells to create heart muscle cells, which then became the first beating cells at the UMC. This sparked my enthusiasm. I have now been researching PLN for ten years.”

Status research

With the first heart tissue we received from the Heart Bank, we have already succeeded in mapping how much stress the heart muscle cells experience, how much PLN-R14del protein accumulation there is in a heart, and whether there is (premature) cell death. The hearts were all analysed in the same way: by reading heart stains, we can say something about the different proteins formed by the cells. The pathology department of the UMC, the PLN Foundation and our colleague Tess Beekink are assisting us in this. We have already been able to establish that PLN-related protein accumulations have been found in people who do not yet suffer from PLN-related symptoms. This means that something is already happening in the body before someone develops symptoms. This is helping us to understand the disease a little better and we already have some potential treatments in mind, such as gene therapy.

I need more hearts

As a researcher, I am very pleased with the Hartenbank. The tissue we needed for our research was available quickly. We submitted our request in the autumn; we received the tissue in October and were able to present our initial findings at a conference in Philadelphia in November. We greatly appreciate the work of the biobank staff. They sometimes even work evenings or weekends to prepare the tissue for research. That is an enormous amount of valuable work. We need more hearts for further research. In total, we want to use at least dozens of them for our research and continue to supplement our data.”

Do you want to know more about PLN?

Please have a look on the website of PLN: Stichting PLN – Samen werken we PLN de wereld uit! (plnheart.org)

In this video Renee Maas tells about the importance of the Hartenbank.

Heeft u ook een genetische hartaandoening en wilt u zich opgeven voor het onderzoek van de Hartenbank? Dat kan hier.