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: 8507557
• 负责人: William Robert Taylor
• 金额: $ 35.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507557
• 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; receptor for advanced glycation endproducts

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.

如今，糖尿病在美国是一个爆炸性的重大公共卫生问题，直接影响心血管疾病的发病率和死亡率。这些破坏性心血管并发症的主要原因之一是糖尿病患者的侧支血管发育受损。功能性侧支血管的形成是人类对血流阻塞的主要适应机制。在这个项目中，我们将探讨晚期糖基化终末产物和晚期糖基化终末产物的特异性受体（RAGE）在抑制侧支血管形成中的作用。我们已经开发出令人兴奋的初步数据，表明高级糖基化终产物可显着抑制侧支血管的形成。此外，我们 已经提供了初步数据，证明单核细胞中 RAGE 信号传导在此过程中的核心作用。拟议的研究将首先检查 RAGE 在抑制侧支血管形成中的总体作用。后续目标将研究 RAGE 在单核细胞和 T 细胞中的具体贡献，因为我们和其他人已经证明这两种炎症细胞类型对于侧支血管的形成至关重要。其他研究将探讨活性氧作为单核细胞和 T 细胞 RAGE 信号转导中关键信号中间体的作用。通过这些研究，我们将 对 RAGE 信号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的评估。