Millions in EU funding for study on the smallest blood vessels in the heart and brain.

Researchers at Maastricht UMC+ are receiving almost one and a half million euros in funding to study the possible mutual causes of vascular dementia and heart failure. The theory is that a reduction in the number of small blood vessels lies at the root of both disorders. The researchers hope to improve diagnosis and discover new leads for treatment by working with colleagues at other European knowledge institutions. A total of six million euros will be made available for the project (under the supervision of Leuven University).

Medical disorders seldom occur on their own and are often interrelated. Obesity and high blood pressure, for example, are commonly associated with cardiovascular diseases. The presence of more than one disorder in the same person is called a comorbidity. The heart and brain seem to be particularly sensitive to this. For example, patients who suffer from heart failure are more likely to have cognitive problems than healthy people, and risk factors for heart failure also contribute to memory impairment. It seems, then, that similar mechanisms underpin disorders of the brain and the heart.

Minuscule blood vessels

The research project that has just received funding will focus on the mutual causes of heart failure and vascular dementia. In both cases, damage to the smallest blood vessels appears to be the root cause. High blood pressure and the natural process of ageing impair the quality of this ‘microcirculation’. The current study is investigating the hypothesis that the number of vessels also declines. By combining different research techniques, the researchers hope to gain more clarity about the consequences of these changes in the small blood vessels.

Clinical and basic research

The research project has been divided into different components. In the clinical component, the researchers will use advanced MRI techniques to trace the smallest blood vessels in the brain and heart of patients with incipient heart failure and incipient vascular dementia and to monitor changes over time. The clinical component will be the specific focus of the Maastricht UMC+ researchers. The component focusing more on basic research involves studying molecular mechanisms that may be responsible for the disappearance of the smallest blood vessels. The findings could provide leads for new forms of treatment.

Paying better attention

‘Very little research is being done into the relationship between pathologies of the heart and the brain,’ says Prof. Robert van Oostenbrugge, head of Neurology at Maastricht UMC+, ‘even though there are growing indications of a close connection. Often, we still focus too much on one disorder, for example heart failure, when in fact we should be paying better attention to the potential long-term consequences for the brain. We hope that this new study will show that microcirculation plays an important role in this process.’

The research project has been named CRUCIAL and is funded by the EU’s Horizon 2020 programme. Researchers participating in the project on behalf of Maastricht UMC+ are Prof. Walter Backes and Dr Jaap Janssen (Radiology), Prof. Robert van Oostenbrugge and Dr Julie Staals (Neurology) and Prof. Jos Prickaerts and Dr Sebastien Foulquier (Neuroscience).

Researchers at KU Leuven are leading a new 6 million euro project that will investigate a possible common cause of heart disease and dementia. The aim is to improve diagnosis of both diseases, and identify new options for treatment.

The starting point is an observation that people with conditions such as high blood pressure and obesity, or who are simply getting old, have a higher risk of certain kinds of dementia and heart disease. In particular, they seem to have a greater chance of developing vascular dementia, which is associated with reduced blood flow to the brain, and diastolic heart failure, which happens when the heart muscle cannot relax properly.

Conditions such as high blood pressure and obesity can exacerbate diseases, and therefore they are referred to as co-morbidities. “It’s not known why people with these conditions are more likely to get these diseases, nor why the heart and brain are especially sensitive,” explains Professor Elizabeth Jones, from the Department of Cardiovascular Sciences, who is coordinating the project. “But one theory is that all of these co-morbidities lead to a loss in the smallest blood vessels, or micro-circulation, around these organs.”

The CRUCIAL project, funded by the European Union’s Horizon 2020 programme, will investigate this theory through fundamental research in the laboratory, and clinical research with patients.

The fundamental research will work towards understanding why blood vessels are being lost. “They don’t die from lack of blood flow,” says Professor Jones. “Instead, the blood stops flowing after the vessels disappear.”

Her group at KU Leuven will explore this further by looking at the molecular pathways that maintain the micro-circulation. “There are pathways being activated that actively make the vessels regress,” she says. “If we can stop that from happening, we can inhibit the loss of the microvessels.” This may open the way for new treatments.

The VIB-KU Leuven Center for Cancer Biology will examine the metabolic changes involved in the loss of micro-circulation. And Maastricht University Medical Centre will look at biological ageing, with a focus on dementia.

On the clinical side, the aim is to see if advanced magnetic resonance imaging (MRI) techniques can be validated as a way of measuring micro-circulatory health. “The important difference is that we are not trying to diagnose the disease, but the loss of blood vessels that we think is the cause,” says Professor Jones.

This imaging will be carried out in a large and varied population of patients, at the Academic Hospital Maastricht, the Universidad de Navarra, and University College London. Doctors who are routinely scanning patients’ hearts will be asked to examine their brains at the same time, and vice versa. This is not common practice at present. And the MRI techniques will be standardised across all the hospitals, so that the results are comparable.

“We are hoping to bring the imaging to the point where it can be diagnostic, to move these academic MRI techniques into clinical practice,” Professor Jones says. This will give doctors an important new way to personalise patient care. “Just because you have co-morbidities doesn’t mean that you will experience heart failure or dementia. So by improving the imaging technology, we hope we will be able to identify who is at risk and needs to be monitored more closely.”

At the same time, the researchers will look at alternatives to MRI that may give comparable results at lower cost. For example, optical coherence tomography angiography measures the micro-circulation in the eye. “The idea is that the eye is part of the nervous system, so if your nervous system is losing blood vessels then so will the retina, at the back of the eye.” The microcirculation can also easily be measured under the tongue, using a technology called Glycocheck. “If the loss of blood vessels is not specific to heart and brain, we may be able to identify it there as well.”

Other options involve looking at microvesicles, which are fragments of cell membrane that circulate freely in the body, or at a range of biomarkers in the blood. “These technologies have been used before to look at micro-circulation, but they have never before been assessed against MRI results.”