Matrix Metalloproteinases in Kawasaki Disease

川崎病中的基质金属蛋白酶

• 批准号: 7247226
• 负责人: JANE C BURNS
• 金额: $ 10.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7247226
• 关键词: Acute; Affect; Alleles; Aneurysm; Arterial Fatty Streak; Atherosclerosis; Blood Vessels; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Cell physiology; Cells; Cessation of life; Child; Childhood; Clinical; Clinical Research; Coronary Aneurysm; Coronary artery; Data; Detection; Development; Diagnostic; Diagnostic tests; Disease; Endopeptidases; Endothelial Cells; Etiology; Extracellular Matrix; Extracellular Matrix Degradation; Family; Fever; Genes; Genetic Polymorphism; Genetic Transcription; Goals; Grant; Haplotypes; Infant; Injury; Interstitial Collagenase; Intracranial Aneurysm; Intravenous Immunoglobulins; Invasive; Laboratories; Lead; Link; Linkage Disequilibrium; Matrix Metalloproteinase Inhibitor; Matrix Metalloproteinases; Measures; Mediating; Medical Students; Mentors; Metalloproteinase Gene; Microsatellite Repeats; Mid-Career Clinical Scientist Award (K24); Mucocutaneous Lymph Node Syndrome; Parents; Pathogenesis; Patients; Pattern; Play; Population; Predisposition; Proteins; Research Project Grants; Research Training; Role; Ruptured Aneurysm; Students; Testing; Time; United States; United States National Institutes of Health; Vasculitis; Work; disorder prevention; insight; transmission process

DESCRIPTION (provided by applicant): Kawasaki disease (KD) is the most common cause of acquired cardiovascular disease in childhood in the United States. KD presents a unique dilemma for the clinician: the disease may be difficult to recognize, there is no diagnostic laboratory test, there is an extremely effective therapy, and there is a 25% chance of serious cardiovascular damage or death if the therapy is not administered. Matrix metalloproteinases (MMPs) are secreted by cells in the vascular wall and degrade components of the extracellular matrix (ECM). MMPs have been implicated in atherosclerosis, plaque rupture, and aneurysm formation and polymorphisms in these genes have been associated with susceptibility to atherosclerosis and aneurysm formation. The short-term goals of the PI are to study children with KD as a unique population in which to explore the role of MMPs in vascular damage and the association of MMP polymorphisms with aneurysm formation. The following hypotheses will be tested: 1) MMPs play a key role in injury and remodeling of the vessel wall in children with KD, 2) Pattems of MMP activation and detection of ECM degradation products may be used as a diagnostic test for KD, and 3) Polymorphic MMP alleles are associated with increased susceptibility to KD and with aneurysm formation. This work will lead to new insights into the role of MMPs in KD and general mechanisms of aneurysm formation. Data from this project will be used to determine if there is a role for MMP inhibitors in the treatment of children with KD. The long-term goals of the PI are to understand the pathogenesis and etiology of KD, which will lead to more specific treatment strategies and disease prevention. The PI will mentor two new fellows in clinical research projects related to treatment of IVIG non-responders and non-invasive studies of endothelial cell function. Other trainees (graduate and medical students) will be involved in KD-related clinical projects. The PI will mentor two new UCSD medical students each summer on the NIH Student Research training grant at UCSD. This K24 award will allow the PI to relinquish administrative responsibilities and to share clinical responsibilities with the fellows to allow more time for mentoring activities.

描述（由申请人提供）： 川崎病 (KD) 是美国儿童获得性心血管疾病的最常见原因。 KD 给临床医生带来了一个独特的困境：这种疾病可能难以识别，没有诊断性实验室测试，没有极其有效的治疗方法，如果不进行治疗，有 25% 的机会出现严重心血管损害或死亡。基质金属蛋白酶 (MMP) 由血管壁细胞分泌并降解细胞外基质 (ECM) 的成分。 MMP 与动脉粥样硬化、斑块破裂和动脉瘤形成有关，这些基因的多态性与动脉粥样硬化和动脉瘤形成的易感性相关。 PI 的短期目标是将患有川崎病的儿童作为一个独特的人群进行研究，以探索 MMP 在血管损伤中的作用以及 MMP 多态性与动脉瘤形成的关系。将测试以下假设：1) MMP 在 KD 儿童血管壁损伤和重塑中发挥关键作用，2) MMP 激活模式和 ECM 降解产物检测可用作 KD 的诊断测试，以及3) 多态性 MMP 等位基因与 KD 易感性增加和动脉瘤形成相关。这项工作将为 MMP 在 KD 中的作用和动脉瘤形成的一般机制带来新的见解。该项目的数据将用于确定 MMP 抑制剂在治疗川崎病儿童中是否有效。 PI的长期目标是了解川崎病的发病机制和病因，这将有助于制定更具体的治疗策略和疾病预防。 PI 将指导两名新研究员从事与 IVIG 无反应者治疗和内皮细胞功能非侵入性研究相关的临床研究项目。其他学员（研究生和医学生）将参与与 KD 相关的临床项目。每年夏天，PI 将利用 UCSD 的 NIH 学生研究培训补助金指导两名新的 UCSD 医学生。 K24 奖项将允许 PI 放弃行政责任，并与研究员分担临床责任，以便有更多时间进行指导活动。