Microvascular Alterations in Diabetic Mice Correlate With Level of Hyperglycemia

Abstract

Vascular alterations are the most common causes of morbidity and mortality in diabetic patients. Despite the impact of endothelial dysfunction on microcirculatory properties, little is known about the endothelial cell alteration during the development of diabetes and its correlation to the metabolic situation. For that reason we continuously monitored in vivo functional and morphological alterations of the microvasculature in hyperglycemic and hyperinsulinemic transgenic UCP1/DTA mice with brown fat deficiency, using a dorsal skin-fold chamber preparation and fluorescence microscopy. UCP1/DTA mice showed a dramatic decrease in vascular density due to a remarkable reduction of small vessels. Vascular permeability and leukocyte endothelial interactions (LEIs) significantly increased. The extent of vascular alteration correlated with the extent of metabolic dysfunction. Decreased tissue perfusion observed in UCP1/DTA mice might play a role in impaired wound healing observed in diabetes. The increased permeability in subcutaneous tissue may serve as predictor of vascular changes in early stages of diabetes. The increased LEI and serum tumor necrosis factor-α levels, which mirror the inflammatory process, support the growing evidence of the inflammatory component of diabetic disease. The results suggest that anti-inflammatory strategies might be able to prevent vascular deterioration in early stages of diabetes. Further investigations are required to evaluate the benefit of such therapeutic strategies.