In the Netherlands, around 1.7 million people have cardiovascular disease. This can have a significant impact on patients’ daily lives. For example, people with heart failure, where the heart cannot pump blood properly, become tired and short of breath very quickly, and often have difficulty climbing stairs or riding a bicycle. Heart disease sometimes leads to hospitalization or death. Since there is still a lot of uncertainty about the origin of various heart diseases, Maastricht researchers from the CARIM research institute want to understand this better in order to prevent the disease and enable targeted treatment.
Genetic variation in the blood
Job Verdonschot, researcher and clinical geneticist in training, will study the genetic changes in blood cells to better understand heart failure. In heart failure, the heart no longer pumps blood properly. He studies how changes in these genes contribute to an inflammatory response in the body that ultimately affects the heart muscle. Verdonschot explains: ‘We see that patients with heart failure often experience swelling during sleep, but we still don’t know much about the reasons. It has recently been discovered that changes in blood cell genes may play a role. Although such genetic changes occur without problems in many people, we think that large changes cause inflammation and are therefore part of the disease mechanism.’ So Verdonschot goes into one a large database of patients with diastolic heart failure study how often these genetic changes occur. He also studies inflammation in mice with this genetic change. ‘We want to find out if anti-inflammatories can help reduce symptoms and reduce the progression of heart failure in people with this mutation in the blood cells, and which anti-inflammatories are best to choose.’
Different types of inflammation
Vanessa van Empel, cardiologist and researcher, will study how heart failure can be prevented or reduced. She also looks at the role of inflammatory reactions. “We want to find out if there are subgroups of patients with their own inflammatory mechanism, and if that affects how the heart works. If the inflammatory response is different, the best treatment may also be different. ” Van Empel previously established a large database with data from patients with heart failure for scientific research – the database with which Verdonschot also hopes to answer his research questions. She is now going to expand that database further: ‘We are going to call all the patients in our database again for blood samples. We remove the white blood cells from there to further investigate the inflammatory response.’ The ultimate goal is to find a better cure for heart failure.
Let the heart muscle repair itself
Leon de Windt, a professor of molecular biology, aims to help heart muscles repair themselves after a heart attack. “During a heart attack, the heart muscle is damaged because too much oxygen is not flowing to it, usually because of a blocked blood vessel,” said De Windt. “The problem is that the heart muscle can’t repair itself, so a heart attack causes permanent damage to the heart. But some animals, such as zebrafish and African spiny mice, can do this.’ De Windt wants to find out which genes are responsible for this ability of heart muscle to repair itself. With this knowledge, he wants to develop gene therapy and investigate whether the natural ability of the human heart can repair itself. He will test this on organoids, miniature versions of the human heart made from human stem cells, and on slices of human heart muscle.
Sudden increase in heart failure
Miranda Nabben, an assistant professor specializing in cardiac metabolism, will focus on the treatment of suddenly worsening heart failure. When patients with heart failure experience symptoms such as shortness of breath over a short period of time, this is called acute decompensation of heart failure. People often have to go into the hospital for this, but there is still no good treatment. This is because the cause of the growth is not clear, but there are symptoms. Nabben explains: ‘Changes in certain metabolic proteins seem to play an important role in the worsening of heart failure. A new drug that counteracts these protein changes has led to improved heart function in laboratory animals.’ Her research in rats with heart failure focuses on understanding the disturbances in these proteins. “We first want to understand the development of the disease and study how medicine can respond to these changes. We do this at different times to find out when the treatment is most effective.’ In addition to her research on rats, Nabben also uses organoids to study heart failure in human cells. ‘In this way we hope to find a drug that will reduce the deterioration of heart failure.’
Reversing a disturbed inflammatory response
Marleen van Greevenbroek, medical biologist and epidemiologist, will study how the body restores balance after an inflammatory response. An inflammatory response appears to play a role in people who are properly treated for risk factors such as high blood pressure or high cholesterol, but still develop cardiovascular disease. “Although medications may reduce the inflammatory response and therefore prevent or repair vascular damage, they increase the risk of infection,” explained van Greevenbroek. ‘That’s why we don’t focus on suppressing the inflammation, but on stopping the inflammation once it’s done its job.’ She looks at specific substances in the blood that promote recovery after inflammation. These substances are called ‘specific proresolvin mediators’. With data out The Maastricht Study we investigate whether people who have a lot of these substances in their blood have a lower risk of cardiovascular disease. We also look at the genes involved in the production and function of these substances, to see if they play a role in the risk of cardiovascular disease. By understanding the way the body resolves the inflammatory response, it can help reduce the risk of cardiovascular disease.
ERA4Health promotes international research by providing subsidies to European collaborations, including in the field of cardiovascular diseases. The research by Job Verdonschot and Vanessa van Empel uses data from a large database that received financial support from the Limburg Heart and Vascular Research Fund was raised.
2024-04-28 10:05:50
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