Date of Award
Master of Science (MS)
Edward C. Carlson
Damage to small blood vessels in diabetes mellitus (DM) is largely the result of hyperglycemia-driven oxidative stress. This is manifested morphologically by capillary basement membrane (BM) thickening, the hallmark feature of chronic complications of DM. In an effort to demonstrate pulmonary alveolar BM (PABM) thickness increase in DM and to demonstrate for the first time, mitigation of the increase utilizing antioxidant therapy, we crossed the severely diabetic transgenic mouse (OVE) with Jtmt, our recently developed transgenic animal model that overexpresses the antioxidant metallothionein (MT) in endothelial cells. Unbiased TEM morphometry demonstrated that PABM widths in diabetic (OVE) mice were significantly (+20%) thickened. Remarkably, however, the bi-transgenic OVEJtmt progney exhibited statistically significant protection against DM-derived BM thickening. These results provide evidence for a direct role of oxidative damage to endothelial cells in diabetic mice and show that protection of these cells can reduce one of the primary features of diabetic microangiopathy.
Hewitt, Holly M., "Targeted Overexpression Of Metallothionein In Endothelial Cells Mitigates Pulmonary Alveolar Basement Membrane Thickening In Transgenic Diabetic Ove Mice: An Unbiased Tem Morphometric Analysis" (2013). Theses and Dissertations. 1542.