Why aortic aneurysms occur at the vascular arch or in the abdominal section

Hematoxylin and eosin staining of cross-sections of the mouse abdominal aorta: -
Hematoxylin and eosin staining of cross-sections of the mouse abdominal aorta: - Left: Image of a healthy mouse aorta. Right: image of an aortic aneurysm. Scale bar: 200 micrometers. © Photo: Daniela Wenzel Download all images in original size All rights reserved!
The usual sites where vascular bulges form are predestined for this from the outset, even in healthy people. This is shown by a study conducted by the Bochum and Bonn medical departments. If a vascular aneurysm bursts in the aorta, it poses an acute danger to life. These so-called aortic aneurysms typically form in the same places on the large blood vessel: either on the upper arch or in the abdominal cavity. "We wanted to know why it is always these sites of all places - what distinguishes them from others?" explains Daniela Wenzel, Head of the Department of Systems Physiology at Ruhr University Bochum. Investigations into the gene activity of the innermost vascular layer showed that even in healthy mice there are abnormalities at precisely these sites. The research team reports in the journal Angiogenesis.

In order to find out what distinguishes the repeatedly affected vascular regions from others, Daniela Wenzel and her team from Bochum and Bonn, which is part of the Collaborative Research Center/Transregio 259 "Aortic Diseases", developed a method to specifically examine the endothelium of the aorta: the innermost layer of the blood vessel. It is known from other vascular diseases such as arteriosclerosis that changes occur in this innermost layer long before symptoms appear," says the researcher.

The researchers succeeded in isolating only the endothelial cells of the aorta of healthy mice using a stamping technique under extreme cold. From these small samples, which comprised only around 350 individual cells, they were able to isolate and examine the RNA. They analyzed the gene activity at different sites of the aorta and compared the sites where aneurysms frequently form with those that do not show this tendency.

Genetic abnormalities

"We found certain patterns of upregulated genes at the sites where aneurysms frequently form," reports Alexander Brückner, a doctoral student in the working group at the Institute of Physiology I at the University Hospital Bonn and the University of Bonn and first author of the study. "These conspicuously active genes influence, for example, changes in the extracellular matrix, the formation of new blood vessels and certain inflammatory reactions." Such genetic abnormalities are also found in tissue from human aneurysms. The researchers also determined the stiffness of the endothelium in the healthy aortic samples together with cooperation partners from the Institute of Physiology at the University of Lübeck. The less elastic the endothelium is, the worse it is for vascular health. They were able to prove that the endothelium was stiffer at the sites where aneurysms frequently develop than at the comparison sites.

Three to four percent of the population between the ages of 65 and 75 suffer from a vascular stenosis of the aorta. Men are affected six times more frequently than women. There is currently no treatment option that can halt the progression of an aneurysm. Only a stent can stabilize the vessel. If an aneurysm bursts, there is a risk to life. Many patients bleed to death before they can receive medical help. If a patient gets to hospital quickly enough, open surgery must be performed - a high-risk procedure.

In the next step, the team used an established model of a knock-out mouse that tends to form aneurysms due to a targeted genetic modification. If high blood pressure is additionally induced in these mice, aortic aneurysms form. They compared the genetic activity in the aortic endothelium of the genetically modified mice without aneurysm with that of mice that had developed an aneurysm due to additional high blood pressure. "In the mice with aneurysms, we found a much greater degree of genetic alterations that belong to the same category as the genetic alterations in healthy mice," says Alexander Brückner. In the mice with an aneurysm, the vessel wall was also altered."

The researchers conclude that the sites where aneurysms frequently form are weak points from the outset. "We don’t know the reasons for this - perhaps it has to do with the mechanical conditions and the blood flow there, or perhaps the altered gene activity at these sites is inherent from birth," explains Daniela Wenzel. The latter seems plausible, as the aorta develops at different heights from different embryonic precursor cells. If risk factors are added to this - such as smoking and high blood pressure - these sites are particularly susceptible to the formation of a vascular sac," explains the doctor.

Through basic research, she hopes to gain a better understanding of the processes that lead to the formation of an aneurysm and thus eventually arrive at approaches for drug treatment.