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

多巴胺在糖尿病内皮细胞功能调节中的作用

基本信息

批准号：
8901151
负责人：
Sujit Basu
金额：
$ 33.17万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-15 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8901151
关键词：
Adult Agonist Amputation Animals Apoptosis Atherosclerosis Blood Circulation Blood Glucose Blood Vessels Blood flow Bone Marrow Bone Marrow Transplantation Caring Cell Proliferation Cell physiology Cells Centers for Disease Control and Prevention (U.S.)Cutaneous Cyclic AMP-Dependent Protein Kinases Data Defect Dermal Diabetes Mellitus Diabetic mouse Diabetic wound Disease Dopamine Dopamine D1 Receptor Dopamine Receptor Doppler Echocardiography Electron Spin Resonance Spectroscopy Endothelial Cells Experimental Designs Functional disorder Glucose Goals Growth Factor Healed Homing Human Immunohistochemistry Impaired wound healing Knowledge Lasers Lead Life Mediating Modeling Monitor Mus NADPH Oxidase Neurotransmitters Oxidases PECAM1 gene Pathway interactions Peripheral Play Process Production Reactive Oxygen Species Refractory Regulation Reporting Role Skin Source Stem cells Streptozocin Stromal Cell-Derived Factor 1 Tissues Tube Up-Regulation Vascular Diseases Wound Healing blood vessel development cytokine density design digital imaging disorder prevention effective therapy endothelial dysfunction healing macrophage neovascularization novel receptor repaired research study tissue culture vascular bed wound

项目摘要

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.

描述（由适用提供）：在糖尿病中，功能失调的内皮细胞（EC）和周围循环中的内皮祖细胞（EPC）数量少，导致几种血管疾病，例如伤口愈合受损。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。由于据报道神经递质多巴胺（DA）调节ROS的产生，并且由于DA也可以控制SDF-1的合成，因此我们假设DA可以在糖尿病伤口组织中正常化EC功能和SDF-1表达。 AIM 1将研究DA D1受体对ROS诱导的EC功能的影响。在AIM 2中，将确定DA D1受体在巨噬细胞产生SDF-1的作用，最后AIM 3将检查DA D1受体对ROS产生和新血管形成在糖尿病伤口组织中的影响。