Collagen-Binding Integrins in Intimal Hyperplasia

内膜增生中的胶原结合整合素

• 批准号: 6612736
• 负责人: ERIC T. CHOI
• 金额: $ 11.66万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612736
• 关键词: blood vessel disorder; cell migration; clinical research; collagen; collagenase; hyperplasia; integrins; laboratory mouse; restenosis; tissue /cell culture; vascular endothelium; vascular smooth muscle

DESCRIPTION (provided by applicant): Candidate Goals and Career Development Plan: The candidate is a vascular surgeon with the long-term goal of becoming an independent investigator in an academic medical center. The candidate has learned skills in the basic research of intimal hyperplasia and of integrin-extracellular matrix (ECM) interactions. This award will provide support needed to develop the foundation of knowledge and skills required for successful long-term investigation. This foundation will be built over the proposed five years of the award by (1) understanding integrin-ECM interactions in vascular disease; (2) determining the interaction of matrix metalloproteinases (MMPs) to the integrin-ECM complex leading to cell movement; and (3) gathering data for the development of an independent project in the pathophysiology of intimal hyperplasia. Environment: The environment is rich in the availability of integrin and extracellular matrix expertise. The candidate's sponsor is well recognized as an independent investigator of ECM and MMPs and has had numerous successes in developing funded independent investigators. The candidate has a well-equipped laboratory and a full-time research technician whose salary is supported by the department. Research Proposal: The primary aim is to investigate the role of integrins in vascular smooth muscle cell (SMC migration and in formation of intimal hyperplasia and restenosis. Preliminary data indicate that beta3 integrin is critical to early SMC migration from aortic explants and early intimal lesion development after arterial injury. Moreover, collagen-binding integrins, alpha1beta1 and alpha2beta1, appear to be critical to late SMC migration from explants. Therefore, we plan to identify the collagen-binding integrin(s) important in SMC-collagen ex vivo and in late SMC migration in vivo. Next, we plan to understand the role of collagenases in the interplay of SMC migration on native collagen. Finally, we will block the critical pathways of SMC migration in vivo to eliminate intimal lesion formation.

描述（由申请人提供）： 候选人目标和职业发展计划：候选人是血管 外科医生的长期目标是成为一名独立研究者 学术医疗中心。候选人已经学习了基本技能 内膜增生和整合素细胞外基质（ECM）的研究 互动。该奖项将提供开发所需的支持 长期成功所需的知识和技能基础 调查。该基金会将在拟议的五年内建立 获奖理由：(1) 了解整合素-ECM 在血管疾病中的相互作用； (2) 确定基质金属蛋白酶 (MMP) 与 整合素-ECM 复合物导致细胞运动； (3) 收集数据 内膜病理生理学独立项目的开发 增生。环境：环境资源丰富 整合素和细胞外基质专业知识。候选人的担保人状况良好 被认可为 ECM 和 MMP 的独立研究者，并拥有众多 成功培养受资助的独立调查员。候选人有一个 设备齐全的实验室和专职研究技术员，工资为 得到有关部门的支持。研究计划：主要目的是 研究整合素在血管平滑肌细胞（SMC迁移）中的作用 并形成内膜增生和再狭窄。初步数据 表明β3整合素对于早期SMC从主动脉迁移至关重要 动脉损伤后外植体和早期内膜病变的发展。 此外，胶原蛋白结合整合素 α1β1 和 α2β1 似乎 对于晚期 SMC 从外植体迁移至关重要。因此，我们计划 体外鉴定 SMC 胶原蛋白中重要的胶原蛋白结合整合素 以及晚期 SMC 在体内的迁移。接下来我们计划了解一下 胶原酶在 SMC 迁移对天然胶原蛋白的相互作用中的作用。最后， 我们将阻断SMC在体内迁移的关键途径以消除 内膜病变形成。