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

描述（由申请人提供）：在糖尿病患者中，外周循环中内皮细胞功能障碍（EC）和内皮祖细胞（EPC）数量不足导致多种血管疾病，如伤口愈合受损。最近的报道表明活性氧（ROS）和细胞因子，基质细胞衍生因子-1¿（SDF-1¿）的低表达是这些病理条件的重要原因。据报道，神经递质多巴胺（DA）可以调节ROS的产生，并且DA也可以控制SDF-1¿的合成，因此我们假设DA可以使糖尿病伤口组织中EC功能和SDF-1¿的表达正常化。目的1将探讨DA D1受体对ROS诱导的EC功能的影响。在Aim 2中，将确定DA D1受体对巨噬细胞产生SDF-1的作用，最后Aim 3将研究DA D1受体对糖尿病伤口组织中ROS产生和新生血管的影响。

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.