Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentLisa S. Ang 1 , Sarah J. Williams 1 , Wendy A. Boivin 1 , Hongyan Zhao 1 , Tyler Varnals 1 ,Bruce M. McManus 1 , Michael F. Allard 1, R. Chris Bleackley 2 , David J. Granville 11James Hogg Research Centre, Providence Heart + Lung Institute, Department of Pathologyand Laboratory Medicine, University of British Columbia, 2 Department of Biochemistry,University of Albertaserpin a3n reduces abdominal aortic aneurysm rupturein mice by inhibition of extracellular granzyme bLisa AngAbstract # 19Backround/ObjectivesAbdominal aortic aneurysm (AAA) is an age-related disease caused by progressive weakening of the vessel wall.Although AAA progression leading to rupture can be fatal, effective pharmacological interventions aimed at haltingAAA progression at early stages of disease are not available. Previous work in our laboratory has demonstrated thatknocking out the serine protease granzyme B (GZMB) reduces incidence and severity of AAA in mice. GZMB is wellknown for its role in eliminating target cells via apoptosis, but also accumulates extracellularly during inflammationand has been shown to cleave extracellular matrix (ECM) components such as fibronection and fibrillin-1. The murineserine protease inhibitor, serpin A3N, has recently been identified as a novel and potent (IC50