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.
Currently the 13th leading cause of death in North America, AAA has an 80 – 90 per cent chance of fatality if the aneurysm ruptures. Ruptured AAA and complications of surgical treatment are responsible for at least 15,000 deaths each year in the United States. However, as autopsies are not routinely performed for people over the age of 60, it is suggested that the actual rate may be as high as 30,000 deaths per year – a mortality rate close to that of prostate and breast cancers. Currently, the only effective treatment interventions involve surgical repair at late stages of disease. There are no treatments for smaller, earlier-stage aneurysms beyond basic monitoring of progression.
"As an aging-related disease, the incidence of AAA is on the rise, yet there are currently no early treatment options beyond basic monitoring of progression and surgery when the risk of rupture is greater than the risk of surgery," says Dr. Granville. "Our latest findings about Granzyme B could lead to the development of pharmaceuticals geared towards slowing or preventing aneurysm progression and rupture – helping those with AAA avoid surgical treatment, and possibly death."
Several patents have been filed relating to Dr. Granville's research. This has led to the formation of spin-off company viDA Therapeutics (www.vidatherapeutics.com), an early-stage biotechnology company spearheaded by President and CEO Alistair Duncan, which is developing first-in-class drugs for the treatment of age-related chronic inflammatory conditions.
Dr. Granville, Ph.D., is an Associate Professor at the University of British Columbia and the Providence Heart and Lung Institute at St. Paul's Hospital. In 2004, he was chosen as one of Canada's Top 40 Under 40 by Caldwell Partners International and will be receiving a Top Forty Under 40 award by Business in Vancouver on January 28. His research is funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of BC & Yukon.
The Providence Heart + Lung Institute at St. Paul's Hospital merges and integrates all of Providence Health Care's heart and lung research, education and care programs, making it the only one of its kind in Canada. www.heartandlung.ca.
Brian Lin | EurekAlert!
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences