Discovery Links Enzyme With Atherosclerosis and Aging

Vancouver, November 5, 2007 — Providence Health Care researcher Dr. David Granville has made a series of discoveries that could have a major impact not only on the treatment of cardiovascular disease, but also on other conditions associated with aging, including hair loss.
Dr. Granville presented his findings yesterday at the American Heart Association Scientific Sessions in Orlando, Florida—the world’s largest gathering of heart researchers —as a finalist for the Louis N. and Arnold M. Katz Basic Science Research Prize.

The key to his discoveries is new knowledge of granzyme B, an enzyme that plays an important role in the immune system. In studies of human tissue conducted at the Providence Heart and Lung Institute at St. Paul’s Hospital, Dr. Granville’s research team found that levels of granzyme B were significantly elevated in patients with atherosclerosis.

Using mouse models of aging and atherosclerotic disease, Dr. Granville and his research team discovered when this enzyme’s expression was blocked, atherosclerosis could be reduced by over 70 per cent. Atherosclerosis is the underlying cause of most heart attacks, strokes, aneurysms and complications arising from diabetes. It is the world’s leading cause of death in those over 60.

Graduate student Rani Cruz also discovered that granzyme B may play a role in hair loss and aging. During experiments in which the expression of this enzyme was blocked in mice they did not appear to age, developed much denser fur and had a significantly longer lifespan.

Granzyme B is released by many immune cells to target and destroy virus-infected cells. Until recently, it was thought that immune cells delivered granzyme B directly into cells targeted for destruction. But Dr. Granville has demonstrated that in certain conditions it is also released by immune cells into the space around healthy cells and in the plasma.

When this occurs, it destroys key structural proteins that surround the healthy cells, which Dr. Granville compares to termites eating away at the infrastructure of a home. This can lead, for example, to a loss of the structural integrity and elasticity of blood vessels and ultimately, atherosclerosis. Dr. Granville is working with UBC and has filed a number of patents related to this research.

Dr. Granville, Ph.D., is an Associate Professor/Canada Research Chair/MSFHR Scholar at the University of British Columbia and the, Providence Heart and Lung Institute at St. Paul’s, part of the Providence Health Care Research Institute. In 2004, he was chosen as one of Canada’s Top 40 Under 40 by Caldwell Partners International. His research is funded by the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research and the Heart and Stroke Foundation of BC & Yukon.


Gavin Wilson
Providence Health Care Communications
Tel. 604-806-8583