An aortic aneurysm, a disease in which the aorta expands into a balloon-like bulge, carries an increased risk of onset with age and is a serious condition that can lead to sudden death if it ruptures. Currently, there is no effective drug treatment available, making surgery the primary method of treatment. In recent years, "clonal hematopoiesis," a phenomenon where specific blood cells with genetic mutations increase in hematopoietic cells as a person ages, has been drawing attention as a new risk factor for cardiovascular diseases.
A research team including Assistant Professor Yoshimitsu Yura of Cardiology at the Nagoya University Graduate School of Medicine focused on the link between abdominal aortic aneurysms and clonal hematopoiesis. By analyzing DNA extracted from the blood of patients scheduled for abdominal aortic aneurysm surgery, they demonstrated that the expansion rate of abdominal aortic aneurysms is faster in patients with clonal hematopoiesis. Furthermore, through experiments using mice, they clarified that clonal hematopoiesis promotes the expansion of abdominal aortic aneurysms. They also discovered that immune cells carrying a mutation in Tet2, one of the causative genes of clonal hematopoiesis, acquire properties similar to bone-resorbing cells and break down elastin, a protein that maintains the elasticity of blood vessel walls, thereby worsening abdominal aortic aneurysms. In addition, they found that suppressing the signal transduction involved in this process, either through genetic methods or inhibitors, can inhibit the progression of abdominal aortic aneurysms in animal models.
The results of this study capture the pathology of abdominal aortic aneurysms from a fresh perspective of the age-related changes in blood and pave the way for the development of medical (non-surgical) treatment strategies. It may also prove useful for the follow-up care of patients with clonal hematopoiesis.
(Article: Masanori Nakajo)
In the aortic wall, the elastin (indicated by the arrows) is thinner and exhibits more breaks (right).