New research findings from a team at the Providence Heart + Lung Institute at St. Paul's Hospital and the University of British Columbia (UBC) may lead to new treatment options for abdominal aortic aneurysms (AAA) - a potentially fatal disease that currently has no pharmacological treatments.
An aortic aneurysm is a bulging of the aorta, the largest blood vessel in the body. If the aneurysm ruptures, it causes rapid blood loss and a high risk of death. About 75 per cent of all aortic aneurysms occur in the part of the aorta that is located in the abdomen, which supplies blood to the lower limbs.
Published in today's American Journal of Pathology, a study led by Dr. David Granville, a researcher with UBC and the Providence Heart + Lung Institute, reveals a novel therapeutic target for AAA that could have a major impact on the treatment of this disease.
Using experimental models of AAA, Dr. Granville and his team identified a protein-degrading enzyme called Granzyme B that is abundant in aneurysms. To determine whether Granzyme B was contributing to aneurysms, the enzyme was genetically knocked out.
"When we removed Granzyme B, we found that it not only slowed the progression of aneurysms, but also markedly improved survival," says Dr. Granville. "This suggests that drugs designed specifically to target Granzyme B could be an effective means of treating aneurysms."
Granzyme B is released by many types of immune cells to target and destroy unwanted or virus-infected cells.
Until recently, it was thought that immune cells delivered Granzyme B directly into cells targeted for destruction, but Dr. Granville's team demonstrates that, in certain conditions, this protein can leak out into the space surrounding healthy cells and in the blood stream. As it builds up outside of cells it starts breaking down structural proteins that maintain tissue integrity - similar to a termites eating away at the infrastructure of a home. In the case of the aorta, this can lead to a weakening of the structure, ballooning of the aorta (creating an aneurysm) and ultimately, the rupturing of the aneurysm.