The incidence of cardiomyopathy and cardiac fibrosis is markedly increased in patients with diabetes mellitus. As cardiac fibrosis is mediated by myofibroblasts, we investigated the effect of diabetes-associated collagen glycation on the conversion of cardiac fibroblasts to myofibroblasts.
Collagen glycation was modeled by the glucose metabolite, methylglyoxal (MGO). Cells cultured on MGO-treated collagen exhibited increased activity of the α-smooth muscle actin (SMA) promoter, elevated levels of collagen I, α-SMA mRNA, and enhanced protein expression of α-SMA, ED-A fibronectin and cadherins. Increased expression of α-SMA was dependent on β1 integrins and on TGF-β. In collagen gel assays, MGO-collagen promoted faster contraction and cell migration was increased by MGO-collagen. In shear-force detachment assays, cells on MGO-collagen were less adherent, and β1 integrin activation and focal adhesion formation were inhibited. We conclude that collagen glycation augments the formation and migration of myofibroblasts, critical processes in the development of cardiac fibrosis in diabetes.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/24289 |
| Date | 07 April 2010 |
| Creators | Yeung, Amy |
| Contributors | McCulloch, Christopher, Simmons, Craig Alexander |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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