Researchers find out why aortic aneurysms form in the arch or abdominal segment

Enlarged vessels in the aorta can be life-threatening if they rupture. So-called aortic aneurysms usually form in the same places in the large blood vessel: either in the upper arch or in the abdomen.

"We wanted to understand why these particular sites are affected. What makes them different from others?" says Professor Daniela Wenzel, head of the Department of Systems Physiology at the Ruhr University Bochum, Germany.

A study of gene activity in the innermost layer of blood vessels showed that even in healthy mice, abnormalities occur in these areas. The research team published their findings in the journal Angiogenesis on July 4.

Stamping technique facilitates endothelial RNA analysis

To find out what distinguishes the repeatedly affected vascular areas from others, Wenzel and her team from Bochum and Bonn, who are part of the Collaborative Research Center/Transregio 259 "Aortic Diseases," developed a method to specifically study the aortic endothelium, which is the innermost layer of the blood vessel.

"We know from other vascular diseases, such as atherosclerosis, that changes in this inner layer occur long before symptoms appear," says the researcher.

The researchers were able to isolate only aortic endothelial cells from healthy mice using a cold-stamping technique. From these small samples, which contained only about 350 individual cells, they were able to isolate and study the RNA. They analyzed genetic activity in different areas of the aorta and compared areas where aneurysms often form with those that do not.

Genetic abnormalities

"We identified specific patterns of activated genes at sites where the extensions often form," explains Alexander Bruckner, a PhD student in the working group of the Institute of Physiology I at the University Hospital Bonn and the University of Bonn, and first author of the study. "These unusually active genes influence, for example, changes in the extracellular matrix, the formation of new blood vessels and certain inflammatory reactions."

Such genetic abnormalities have also been found in human aneurysm tissue. Together with colleagues from the Institute of Physiology at the University of Lübeck, the researchers also determined the stiffness of the endothelium in healthy aorta samples. The less elastic the endothelium, the more harmful it is for vascular health. They showed that the endothelium was stiffer in areas where aneurysms often develop than in control areas.

In the next step, the team used an established knockout mouse model that is prone to forming aneurysms due to targeted genetic modification. When these mice are additionally given high blood pressure, aortic aneurysms form. They compared the genetic activity in the aortic endothelium of genetically modified mice without aneurysms with the activity in mice that developed aneurysms due to the added high blood pressure.

"In the mice with aneurysms, we found a much higher degree of gene changes in the same category as the gene changes in healthy mice," Brueckner says. "The aneurysm mice also had changes in the vessel wall."

The researchers concluded that the sites where aneurysms often form are weak points to begin with. "We don't know exactly why this happens - it may be related to the mechanical conditions and blood flow in these areas, or perhaps altered gene activity in these areas is inherited from birth," Wenzel explains.

The latter seems plausible, since the aorta develops at different levels from different embryonic precursors. "If risk factors such as smoking and high blood pressure are added to this, these areas are particularly vulnerable to the formation of a vascular aneurysm," the doctor emphasizes.

She hopes that basic research will lead to a better understanding of the processes that contribute to aneurysm formation, and that this will ultimately lead to new approaches to drug treatment.