Date of Award


Degree Type


Degree Name

Master of Science




Dr. J. Geoffrey Pickering

Second Advisor

Dr. Murray W. Huff

Third Advisor

Dr. Caroline Schild-Poulter


Senescence of vascular smooth muscle cells (SMCs) has been identified as a feature of atherosclerosis. However, the factors that lead to premature SMC senescence are not well understood. Plaque SMCs reside within a milieu of type I collagen fibrils that, over time, undergo progressive intermolecular cross-linking. This renders the protein resistant to proteolysis. I hypothesized that SMC lifespan is determined by the extent to which the surrounding type I collagen can be proteolytically modified. To test this, I studied mice harbouring a targeted mutation rendering type I collagen resistant to collagenase cleavage (Collalrr). I conclude: 1) Collalr7r collagen promotes a premature aging-like syndrome in mice; 2) premature senescence of vascular SMCs and mouse embryonic fibroblasts is accelerated in the presence of Collal"r collagen. These findings suggest a novel crosstalk between cells and the insoluble ECM that lead to age-related deterioration in vascular function, and possibly of other tissues as well.



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