Researchers from the University of Copenhagen have developed a groundbreaking method that allows for the analysis of thousands of proteins in heart tissue. This provides entirely new insights into the characteristics of heart diseases and could pave the way for more targeted treatments.
Each year, cardiovascular diseases affect more than 65,000 Danes - conditions that claim the lives of one in five Danes. Although diagnostic capabilities have improved, we still lack fundamental knowledge about what drives the development of heart diseases.
Today, approximately 672,000 Danes live with a cardiovascular disease, and around 65,600 are affected each year.
One in five Danes dies from a cardiovascular disease - about 12,100 deaths annually.
The number of deaths caused by cardiovascular disease has more than halved since 1995.
Source: The Danish Heart Foundation
Often, these diseases are only detected once visible changes in the heart's structure or function occur. However, research shows that disease processes begin earlier - at the molecular level.
In a new study from the University of Copenhagen, researchers have developed a method that enables the analysis of heart proteins to identify molecular patterns characteristic of heart diseases.
"With this method, we can create a molecular map of what characterizes the disease. We can see what has driven the disease at a molecular level," says Professor Alicia Lundby from the Department of Biomedical Sciences at the University of Copenhagen, lead author of the study recently published in the scientific journal Nature Cardiovascular Research.
"We actually know surprisingly little about what causes and drives heart diseases at the molecular level. But with this method, we can now investigate heart diseases where we lack knowledge about the underlying mechanisms," says Alicia Lundby.
Ultrathin slices of heart muscle
In the new study, researchers mapped the inherited heart disease arrhythmogenic right ventricular cardiomyopathy (ARVC).
To understand the molecular causes of the disease, they closely examined tissue samples from heart patients - so-called biopsies. These biopsies were previously collected during diagnostic procedures the hospitals.
First, they cut ultrathin slices - just one-hundredth of a millimeter thick - from the samples and then performed a proteomic analysis of the slices.
Proteomic analysis allows for the measurement and examination of up to 10,000 different proteins in a single tissue sample, providing a far more detailed picture of the biological basis of the disease than previous methods.
Although proteomic analysis is a known method in scientific research, it has previously been difficult to apply to diagnostically collected heart tissue. These biopsies are handled in ways that previously limited proteomic analysis. The researchers have now overcome this barrier, opening the door to using already collected biopsies to gain new insights into heart diseases.
A foundation for medical treatment
The researchers believe the analysis method can be used to better understand many other heart diseases and their underlying causes.
"Today, we only treat the underlying causes of heart diseases to a limited extent. In order to develop targeted treatments, we need deeper insight into what drives these diseases," says Alicia Lundby, adding:
Today, we only treat the underlying causes of heart diseases to a limited extent.
"For example, heart failure can be caused by fibrosis, inflammation, or changes in mitochondrial function in the heart muscle. The diagnosis is the same - heart failure - but the molecular causes can be vastly different and ideally require different treatment strategies."
The next step for the researchers is to map a broader spectrum of heart diseases and identify their molecular characteristics. The goal is to create a foundation for more targeted medication for heart patients.
"We hope our results can reveal which parts of the protein landscape are misregulated and drive heart disease. Once we have that knowledge, we can investigate whether existing drugs can be used more precisely or use the mapping as a basis for developing new treatments," says Alicia Lundby.
Read the study: "Quantitative proteomics of formalin-fixed, paraffin-embedded cardiac specimens uncovers protein signatures of specialized regions and patient groups".
