INFLAMMATORY MEDIATORS LEAD TO CAROTID PLAQUE INSTABILITY AND RUPTURE

炎症介质导致颈动脉斑块不稳定和破裂

• 批准号: 7959751
• 负责人: Hernan A Bazan
• 金额: $ 7.72万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959751
• 关键词: Accounting; Anti-Inflammatory Agents; Anti-inflammatory; Arterial Fatty Streak; Biology; Cardiovascular system; Carotid Artery Plaques; Carotid Atherosclerotic Disease; Carotid Endarterectomy; Cerebrum; Clinical; Computer Retrieval of Information on Scientific Projects Database; Coronary heart disease; Data; Development; Event; Foundations; Funding; Future; Grant; Immunohistochemistry; Inflammation Mediators; Inflammatory; Institution; Lead; Mentors; Molecular; Molecular Biology Techniques; Morbidity - disease rate; Myocardial Infarction; Omega-3 Fatty Acids; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Proteome; Proteomics; Research; Research Personnel; Research Project Grants; Resources; Role; Rupture; Source; Stroke; Stroke prevention; Testing; Translational Research; United States; United States National Institutes of Health; cost; cytokine; effective therapy; new therapeutic target; novel; therapy development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Carotid and coronary disease lead to stroke and myocardial infarction, respectively, through atherosclerotic plaque rupture. This translational research project aims to investigate in patients with high-grade carotid atherosclerotic disease undergoing carotid endarterectomy (CEA) surgery the biology of unstable and stable plaques and provide the scientific foundation for development of new venues in plaque stabilization. The long-term objective of this project is to define the significance of inflammatory mediators in statin-carotid atherosclerotic plaque stabilization and prevention of stroke and identify potential novel targets for plaque stabilization. Carotid atherosclerotic disease is the third leading cause of stroke in the United States and the morbidity accounts for over $55 billion in societal costs. The mechanism by which a carotid atherosclerotic plaque becomes unstable and causes cerebral or ocular ischemic events is poorly understood. Various groups, including the Investigator, have identified a variety of inflammatory mediators that are associated with vulnerable carotid plaques. These include anti-inflammatory cytokines and omega-3 fatty acids (please see 'Preliminary Results'). These data have led to the hypothesis that there are key molecular differences between stable and unstable carotid plaques. The Specific Aims of this translational research grant are 1) to integrate whole proteome studies with clinical correlates to define the mechanisms of carotid plaque instability and 2) test whether these molecules are associated with statin-drug atherosclerotic plaque stabilization. Our overall aim is to identify potential new venues of atherosclerotic plaque stabilization. Studies in Aim 1 will a) determine novel inflammatory molecules involved in carotid plaque vulnerability and b) aim to identify potentially novel therapeutic targets for plaque stabilization. Powerful experimental approaches, including plaque proteomic analysis, immunohistochemistry, and molecular biology techniques will be used to study the role of various molecules in carotid plaque instability. Studies in Aim 2 will test the hypothesis that the proteomic signature of unstable carotid plaques determines statin-drug atherosclerotic plaque stabilization. We aim for a better understanding of carotid plaque instability and contribute to the development of novel effective therapies. The information obtained in this proposal will provide a framework to rationally examine and direct future therapy development for patients with high-grade carotid atherosclerotic disease.

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