Role of dopamine in the regulation of endothelial cell functions in diabetes

Ohio State University, Columbus OH

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Abstract

DESCRIPTION (provided by applicant): In diabetes mellitus, dysfunctional endothelial cells (EC) and low numbers of endothelial progenitor cells (EPC) in the peripheral circulation lead to several vascular disorders like impaired wound healing. Recent reports indicate reactive oxygen species (ROS) and low expression of the cytokine, stromal cell-derived factor-1? (SDF-1?) to be important causes of these pathological conditions. As neurotransmitter dopamine (DA) is reported to regulate ROS production and because DA may also control SDF-1? synthesis, we therefore hypothesized that DA could normalize EC functions and SDF-1? expression in diabetic wound tissues. Aim 1 will investigate the effect of DA D1 receptors on ROS induced EC functions. In Aim 2, the role of DA D1 receptors on SDF-1? production by macrophages will be determined and finally Aim 3 will examine the effects of DA D1 receptors on ROS production and neovascularization in diabetic wound tissues.