An aortic aneurysm is a pathological aorta enlargement that can result in tearing or rupturing the aorta. It is often life-threatening. The condition is symptomless, often going undiagnosed until it becomes very advanced and requires surgical intervention. Univ. Prof. David Bernhard, Dr. Christian Doppler (both from the Department of Pathophysiology, Institute of Physiology and Pathophysiology, at the JKU’s Faculty of Medicine), along with their team, have been able to learn more about the condition to detect it early and provide individual treatment.

One distinctive feature of this condition is that its onset is often associated with a particular aortic valve morphology. A normal aortic valve is tricuspid, meaning it has three valve leaflets. However, 2% of the population has a bicuspid aortic valve, meaning there are only two valve leaflets. While this bicuspid condition is not pathological per se, up to 80% of those affected will develop an aortic aneurysm during their lifetime. To date, experts still do not fully know why the condition develops.

Univ. Prof. David Bernhard, pathophysiologist and head of the Center for Medical Research at the JKU, explains: "During our study, we tried not to restrict ourselves to local effects as much as we could, however we also wanted to explore the systemic effects. We examined the state of the diseased, affected tissue as well as individual cells we isolated from the affected tissue. By analyzing the blood, we could detect additional full-body changes, again with a goal of identifying potential factors to support early detection. In order to be able to interpret the results accordingly, all of these experiments were also conducted on a healthy control group, meaning those who do not suffer from this disease."

The results reveal massive atherosclerotic changes in the tissue and a disease-related disorder of the lipid metabolism. The experts identified lipid-coupled metabolic pathways that were pathologically altered in the affected cells. These findings may result in detecting the disease earlier. By using various methods (MALDI imaging and staining of tissue sections), scientists not only found that the disease altered the distribution of these lipids in the tissue as a whole, but in the tissue, they were able to identify the responsible enzymes.

Dr. Christian Doppler added: "The most important finding, however, is that there were major differences between the two groups. All of the pathological changes described above appeared exclusively in the group that had a normal, tricuspid aortic valve. The group that has the bicuspid aortic valve did not show any pathological changes, but resembled the healthy control group at the tissue, cellular and genetic levels. These results suggest that symptomatically, this group also has aortic aneurysm, but the cause and pathological development are profoundly different. In the future, this finding could result in individualized treatment."

The final part of the study analyzed blood samples taken from the test subjects which likewise revealed a disease-related increase in specific lipids (phosphatidylcholines, ceramides and acylcarnitines) in the blood. This proves that this apparently local, asymptomatic aortic disease systemically effects the body’s circulation. The study’s findings also provide important approaches to not only help identify markers and detect the disease early on, but also to develop new approaches in treating it.

Univ. Prof. David Bernhard confidently added: "The study provides new insight into how aortic aneurysms develop, opening up new ways to detect it early on and create an individual treatment approach."