权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pathophysiological Activities of Oxidized Phospholipids

氧化磷脂的病理生理活性

基本信息

批准号：
8432820
负责人：
EUGENE A PODREZ
金额：
$ 33.29万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2014-11-03
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8432820
关键词：
Address Adhesions Affinity Agonist Arterial Fatty Streak Atherosclerosis Binding Biological Assay Blocking Antibodies Blood Circulation Blood Clot Blood Platelets Blood coagulation CD36 gene Cells Cholesterol Cytoplasmic Granules Data Development Diabetes Mellitus Disease Dyslipidemias Elements Family Functional disorder Generations Hyperlipidemia In Vitro Investigation Lecithin Ligands Mediating Metabolic syndrome Molecular Mus Oxidative Stress Pattern Recognition Phase Phospholipase A2 Phospholipids Physiological Platelet Activation Play Property Proteins Receptor Cell Recombinants Regulation Risk Risk Factors Role Rupture SR-B proteins SR-BI receptor Signal Transduction Site Solid Staging Testing Thrombosis Toll-like receptors Up-Regulation acute coronary syndrome adduct in vivo macrophage novel overexpression oxidized lipid receptor receptor function response scavenger receptor sensor

项目摘要

A significant role for increased platelet reactivity in the pathophysiology of occlusive arterial thrombosis is widely recognized. However, the mechanisms responsible for enhancing platelet reactivity in vivo during hyperlipidemia are poorly understood. We have recently isolated and structurally defined a novel family of oxidized choline glycerophospholipids (oxPCCD36) that are present in vivo at sites of enhanced oxidative stress. oxPCCD36 serve as high affinity ligands for scavenger receptors class B and modulate platelet reactivity and thrombosis in oxidative stress. Our preliminary studies demonstrated that a class of products formed as a result of degradation of oxPCCD36 by PLA2 (carboxyalkylpyrolle protein adducts) is a new and powerful platelet agonist, however, the receptors mediating its effect are not known. Platelets express a number of receptors with pattern recognition properties, including several toll like receptors (TLRs). A recent study suggested that platelet TLRs may modulate thrombosis when their ligands are present in circulation. This proposal will address the hypothesis that platelet TLRs alone, or in cooperation with scavenger receptors modulate platelet reactivity and prothrombotic state induced by endogenous ligands generated in oxidative stress. This proposal will also pursue the hypothesis that carboxyalkylpyrolle protein adducts serve as novel ligands for platelet scavenger /toll like receptors and identify the mechanisms of prothrombotic activity. Finally, we will continue the investigation of the molecular mechanism of scavenger receptor BI regulation of platelet function and thrombosis in dyslipidemia. Our preliminary data strongly support our hypothesis. The Specific Aims are: Aim1: To assess whether the platelet activating and prothrombotic activities of oxPCCD36 are mediated by platelet TLRs alone, or in cooperation with scavenger receptors class B. Aim2: To investigate the role of scavenger receptor-BI in platelet function in dyslipidemia and oxidative stress. Aim3: To elucidate the mechanism and assess the physiological and pathophysiological consequences of the interaction between carboxyalkylpyrolle protein adducts (CAPs) and platelets.

血小板反应性增高在闭塞性病理生理中的重要作用