Role of inflammatory cell RAGE in collateral vessel formation

炎症细胞RAGE在侧支血管形成中的作用

• 批准号: 7788446
• 负责人: William Robert Taylor
• 金额: $ 40.22万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-13 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788446
• 关键词: Advanced Glycosylation End Products; Adverse effects; Anatomy; Atherosclerosis; Binding; Biological Assay; Blood Vessels; Blood flow; Cardiovascular system; Cell Culture Techniques; Cell physiology; Cells; Complications of Diabetes Mellitus; Coupled; Data; Development; Diabetes Mellitus; Diabetic Angiopathies; Etiology; Exhibits; Gene Expression; Goals; Growth; Histology; Human; Impairment; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Ischemia; Laboratories; Limb structure; Mediating; Modeling; Morbidity - disease rate; Mus; Obstruction; Pathology; Physiological; Play; Process; Production; Public Health; Reactive Oxygen Species; Receptor Cell; Relative (related person); Role; Running; Series; Signal Transduction; Small Interfering RNA; T-Cell Activation; T-Lymphocyte; Therapeutic; United States; Vascular Diseases; cell type; diabetic; diabetic patient; insight; macrophage; monocyte; mortality; nanoparticle; novel strategies; overexpression; pre-clinical; receptor; receptor expression

Diabetes in the United States today is an explosive major public health issue that directly impacts cardiovascular morbidity and mortality. One major reason for these devastating cardiovascular complications is that diabetics exhibit impaired collateral vessel development. Formation of functional collateral blood vessels is the primary adaptive mechanism in humans to blood flow obstruction. In this project we will explore the role of advanced glycation end products and the specific receptor for advanced glycation end products (RAGE) in inhibition of collateral blood vessel formation. We have developed exciting preliminary data showing that advanced glycation end products dramatically inhibit collateral vessel formation. Moreover, we have presented preliminary data that demonstrate a central role for RAGE signaling in monocytes in this process. The proposed studies will first examine the overall role of RAGE in inhibiting collateral vessel formation. Subsequent aims will study the specific contributions of RAGE in monocytes and T cells as these two inflammatory cells types have been shown by us and others to be critical for the formation of collateral blood vessels. Additional studies will examine the role of reactive oxygen species as crucial signaling intermediates in RAGE signal transduction in both monocytes and T cells. Through these studies, we will develop a comprehensive and critical assessment of the role of RAGE signaling in inflammatory cells and the subsequent impact on collateral vessel formation.

今天，美国糖尿病是一个爆炸性的主要公共卫生问题，直接影响心血管发病率和死亡率。造成这些毁灭性心血管并发症的主要原因之一是糖尿病患者表现出副血管发展受损。功能性附带血管的形成是人类对血流阻塞的主要自适应机制。在该项目中，我们将探讨晚期糖基化终产物的作用和高级糖基化终产物（RAGE）在抑制副血管形成中的作用。我们已经开发了令人兴奋的初步数据，表明先进的糖基化最终产物极大地抑制了侧支血管的形成。而且，我们 已经提供了初步数据，这些数据证明了在此过程中单核细胞中愤怒信号传导的核心作用。拟议的研究将首先研究愤怒在抑制副容器形成中的总体作用。随后的目的将研究单核细胞和T细胞中愤怒的特定贡献，因为我们已经表明了这两种炎症细胞类型，而其他炎症细胞类型对于副血管的形成至关重要。其他研究将研究反应性氧作为至关重要的信号传导中间体在单核细胞和T细胞中rage信号转导中的作用。通过这些研究，我们将 对愤怒信号传导在炎症细胞中的作用以及随后对侧支血管形成的影响进行全面和批判性评估。