Dr. David Granville

2003 Career Investigator Award, Scholar

Regulation and role of granzyme B in atheromatous diseases

Atherosclerosis – hardening of arteries – is caused by buildup of plaque inside artery walls. This constricts blood flow and elevates blood pressure, and is the leading cause of heart attacks, stroke and lower limb loss due to poor circulation. There is evidence that immune cells provoke a tightly-regulated form of cell death known as apoptosis (programmed cell death) in atherosclerotic blood vessel walls, which contributes to progression of the disease. While the mechanisms are not clearly understood, the result is a change in the architecture of blood vessel walls that leads to additional plaque build-up and also to plaque instability. The latter increases the danger of pieces of plaque breaking off and potentially lodging in and blocking blood flow in smaller vessels.

In previous work, Dr. David Granville and his research team have found that an enzyme used by the immune system to kill abnormal and infected cells is released in atherosclerotic blood vessels. Dr. Granville is studying the role of this enzyme – granzyme B – in vessel wall restructuring and cell death associated with atherosclerosis and transplant vascular disease. Findings from this research may reveal new opportunities for intervening to prevent or treat these vascular disorders.

Completed award term, June 2008

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