ULTRASONIC TISSUE CHARACTERIZATION OF CARDIAC REMODELING

心脏重构的超声组织表征

• 批准号: 6526708
• 负责人: SAMUEL A WICKLINE
• 金额: $ 35.9万
• 依托单位: BARNES-JEWISH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526708
• 关键词: ACE inhibitors; angiocardioultrasonography; angiogenesis; angiogenesis factor; bioimaging /biomedical imaging; cellular pathology; collagen; fibroblast growth factor; immunocytochemistry; integrins; laboratory mouse; laboratory rat; mathematical model; mechanical stress; mitogen activated protein kinase; myocardial infarction; reperfusion; vascular endothelial growth factors; wound healing

DESCRIPTION (Adapted from Applicant's Abstract): Comprehensive delineation of the process of ventricular remodeling after myocardial infarction requires an integrated systems approach to elucidate relationships among molecular and cellular mechanisms, complex three dimensional ventricular kinematics and mechanical signals (e.g., shear strains), and altered tissue structures and material properties. Under the aegis of this grant, the applicants reported having demonstrated the utility of high resolution ultrasound tissue characterization methods for quantifying structural alterations and material properties involved in cardiac wound healing at the microscopic level. The applicants now seek to establish specific relationships between the physical properties of tissue, and the molecular and cellular mechanisms responsible for remodeling, and in particular to examine the potential salutary but relatively unappreciated role of angiogenesis as a critically component of remodeling. Accordingly, the applicants proposed to determine: 1. the role of angiogenesis during post-infarction cardiac remodeling and the effects of ACE inhibitors on angiogenesis in would healing; 2. molecular signaling mechanisms responsible for angiogenesis and scar tissue would healing that may depend on mechanical cues such as fiber strain, by comparing spatially and temporally matched parametric images of regional contractile function, tissue material properties, cell composition (e.g., myofibroblasts), and immunocytochemistry for selected signaling events such as expression of mitogen activated protein (MAP) kinase, integrins, tissue factor, vascular endothelial growth factor (VEGF) and its receptors (KDR/flk-1); and 3.the effects of selected therapies such as coronary reperfusion to evaluate the "open artery hypothesis," which potentially evokes enhanced angiogenesis, treatment with growth factors such as bFGF to enhance angiogenesis, and the role of integrins in cardiac remodeling, with the using beta3-deficient mice that exhibit impaired would healing.

描述（改编自申请人的摘要）：全面描述 心肌梗死后心室重构的过程需要 综合系统方法来阐明分子和 细胞机制、复杂的三维心室运动学和 机械信号（例如剪切应变）以及组织结构的改变和 材料特性。在这笔赠款的支持下，申请人报告 展示了高分辨率超声组织的实用性 量化结构变化和材料的表征方法 在微观水平上参与心脏伤口愈合的特性。这 申请人现在寻求在物理之间建立特定的关系 组织的特性，以及负责的分子和细胞机制 重塑，特别是检查潜在的有益但相对而言 血管生成作为重塑的关键组成部分的作用未被认识到。 因此，申请人建议确定：1.血管生成的作用 梗塞后心脏重构过程中ACE抑制剂的作用 伤口愈合中的血管生成； 2. 负责的分子信号机制 血管生成和疤痕组织的愈合可能取决于机械 通过比较空间和时间匹配来获得诸如纤维应变之类的线索 区域收缩功能、组织材料特性的参数图像， 细胞组成（例如肌成纤维细胞）和免疫细胞化学 信号事件，例如丝裂原激活蛋白（MAP）激酶的表达， 整合素、组织因子、血管内皮生长因子（VEGF）及其 受体（KDR/flk-1）； 3.所选疗法（例如冠状动脉疗法）的效果 再灌注来评估“开放动脉假说”，这可能会引起 增强血管生成，用bFGF等生长因子治疗以增强 血管生成以及整合素在心脏重塑中的作用，以及使用 缺乏β3的小鼠表现出意志愈合受损。