Leukocyte C2GIcNAcT-I in atherosclerosis

动脉粥样硬化中的白细胞 C2GlcNAcT-I

• 批准号: 7149445
• 负责人: YUQING HUO
• 金额: $ 35.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149445
• 关键词: apolipoprotein E; atherosclerosis; atherosclerotic plaque; cardiovascular injury; carotid artery; cell adhesion; cell adhesion molecules; cell migration; flow cytometry; helper T lymphocyte; hexosyltransferase; inflammation; intravital microscopy; laboratory mouse; macrophage; monocyte; neutrophil; nutrition related tag; pathogenic diet; platelet activation

DESCRIPTION (provided by applicant): Atherosclerosis and its complications are the most common causes of morbidity and mortality. These vascular diseases result from adhesive and signaling interactions among leukocytes, platelets and the vessel wall cells. These cellular interactions are mediated by adhesion molecules, including P, E, L-selectin, P-selectin glycoprotein ligand 1 (PSGL-1), CD43, CD44, integrin CD18, VLA-4, and others. The cellular interactions mediated by these molecules broadly participate in various events in atherosclerosis. To obtain optimal activities, molecules including PSGL-1, CD43 and CD44 need to be modified by the addition of branched O-glycans to their protein structures. These reactions are catalyzed by core 2 1-6-N- glucosaminyltransferase-l (C2GlcNAcT-l), which is a Golgi enzyme in leukocytes. This project is designed to investigate whether C2GlcNAcT-l is crucial for cellular interactions involved in the development of atherosclerosis and its complications. In aim 1, we will investigate the rote of C2GlcNAcT-l in the interactions of mononuclear cells with atherosclerotic arteries. In aim 2, we will investigate the role of C2GlcNAcT-l in the contribution of activated platelets to atherosclerosis. In aim 3, we will investigate the role of C2GlcNAcT-l in the development, progression and regression of atherosclerotic lesions. We will also evaluate the influence of C2GlcNAcT-l in the stability of atherosclerotic lesions. In aim 4, we will investigate the role of C2GlcNAcT-l in the interactions of leukocytes and platelets with injured arteries and in the formation of arterial neointima using an established mouse carotid artery wire injury model. These studies will have significant implications for the inhibition of leukocyte C2GlcNAcT-l in the prevention and treatment of atherosclerosis and its complications.

描述（由申请人提供）：动脉粥样硬化及其并发症是发病和死亡的最常见原因。这些血管疾病是由白细胞、血小板和血管壁细胞之间的粘附和信号相互作用引起的。这些细胞相互作用由粘附分子介导，包括 P、E、L-选择素、P-选择素糖蛋白配体 1 (PSGL-1)、CD43、CD44、整合素 CD18、VLA-4 等。这些分子介导的细胞相互作用广泛参与动脉粥样硬化的各种事件。为了获得最佳活性，包括 PSGL-1、CD43 和 CD44 在内的分子需要通过在其蛋白质结构中添加支链 O-聚糖来进行修饰。这些反应由核心2 1-6-N-葡萄糖胺基转移酶-1 (C2GlcNAcT-1)催化，其是白细胞中的高尔基体酶。该项目旨在研究 C2GlcNAcT-1 对于动脉粥样硬化及其并发症的发展所涉及的细胞相互作用是否至关重要。在目标 1 中，我们将研究 C2GlcNAcT-1 在单核细胞与动脉粥样硬化动脉相互作用中的作用。在目标 2 中，我们将研究 C2GlcNAcT-1 在活化血小板对动脉粥样硬化的影响中的作用。在目标 3 中，我们将研究 C2GlcNAcT-1 在动脉粥样硬化病变的发生、进展和消退中的作用。我们还将评估C2GlcNAcT-l对动脉粥样硬化病变稳定性的影响。在目标 4 中，我们将使用已建立的小鼠颈动脉线损伤模型研究 C2GlcNAcT-1 在白细胞和血小板与受损动脉相互作用以及动脉新内膜形成中的作用。这些研究对于抑制白细胞C2GlcNAcT-1预防和治疗动脉粥样硬化及其并发症具有重要意义。