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!
Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
28.05.2018 | Event News
25.05.2018 | Event News
02.05.2018 | Event News
28.05.2018 | Seminars Workshops
28.05.2018 | Trade Fair News
28.05.2018 | Physics and Astronomy