Dysfunction of the microvascular circulation is determined in diabetes and in trauma where physical damage causes disruption in the normal microvascular tissue. The role inflammatory mechanisms play in regulating normal microvascular function is being investigated. Aims of the research program Atherosclerosis affects diabetic patients in a disproportionate manner when compared to the non-diabetic population. However, in the microcirculation, atherosclerosis is not a consistent feature of ischemic or neuropathic diabetic lesions. The difference in microvascular responses to injury compared to macrovascular injury is poorly understood.
Ischemic injury follows a common pathway in different cell types and has been widely studied.
However, the magnitude of the cellular response to oxidative damage depends upon the cell type examined. This project is designed to e to isolate and culture microvascular arteriolar and venular endothelial cells from specific microvessels from the dermal microvascular bed of the dorsum of the foot in both diabetic and non-diabetic animals. From the same vascular bed corresponding macrovascular arterial and venous endothelial cells will be isolated. It may also be that diabetic microvascular endothelial cells are more compromised in their response to oxidative injury than their non-diabetic equivalent. In this study we propose to determine whether an increase of oxidative damage or a decrease in nitric oxide defense mechanism is responsible for the disproportionate microvascular endothelial cell damage in diabetes.