Alon Hendel, Lisa S. Ang and David J. Granville Pages 95 - 110 ( 16 )
Abdominal aortic aneurysm (AAA) is an age-related disease resulting in aortic wall weakening and dilatation which may progress to the fatal point of abrupt aortic wall rupture. Chronic inflammation is a driving force in the pathogenesis of AAA and extracellular matrix (ECM) proteases are considered central to aortic wall degradation. Considerable effort is dedicated to identifying the proteases responsible as well as the mechanism by which these proteases contribute to disease progression. As such, they are considered important molecular targets for pharmacological intervention. Along with smoking, male gender and family history, aging is a major risk factor for AAA. Examination of age-related changes of the immune system reveals an interwoven relationship between the processes of aging and chronic inflammation, collectively predisposing to AAA development. The present review explores current evidence as to the role of specific ECM proteases in AAA pathogenesis. The contribution of the aging process to disease pathogenesis is also explored to provide the relevant context and highlight key molecular pathways that should be considered while attempting to develop effective treatment approaches.
Abdominal aortic aneurysm, aging, extracellular matrix, inflammation, inhibitors, proteases.
James Hogg Research Centre, St. Paul’s Hospital, University of British Columbia. Rm 166, Burrard Building, 1081 Burrard Street, Vancouver, BC. V6Z 1Y6, Canada.