Anisotropy in Healing Myocardial Scar Tissue

愈合心肌疤痕组织中的各向异性

• 批准号: 7370944
• 负责人: JEFFREY W HOLMES
• 金额: $ 45.45万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-09 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370944
• 关键词: Address; Aneurysm; Animal Model; Anisotropy; Biological Models; Cardiac; Cicatrix; Clinical; Collagen Fiber; Development; Devices; Employee Strikes; Environment; Evolution; Fibroblasts; Funding; Goals; Healed; Hormone Receptor; In Vitro; Infarction; Injection of therapeutic agent; Intervention; Left; Left Ventricular Function; Left Ventricular Remodeling; Mechanics; Modeling; Modification; Molecular; Myocardial; Myocardial Infarction; Myocardium; Pathway interactions; Pattern; Polymers; Property; Reperfusion Therapy; Research; Rupture; Signal Transduction; Steroids; Stimulus; Structure; Testing; Therapeutic; Time; Tissues; Ventricular Function; Ventricular Remodeling; Work; base; design; experience; healing; heart function; improved; in vitro Model; in vivo; innovation; prevent; successful intervention; therapeutic target; therapy design; ventricular assist device

Following myocardial infarction, the mechanical properties of the healing scar are a critical determinant of left ventricular function, infarct expansion, aneurysm formation and rupture, and ventricular remodeling. Until recently, the only therapeutic options for addressing these consequences were pharmacologic. However, in the past few years, the introduction of a range of options for modifying the cardiac mechanical environment has fundamentally altered our options for clinical postinfarction therapy. The dynamic in vivo cardiac mechanical environment is now just as valid a potential therapeutic target as hormone receptors or signaling cascades. In principle, if mechanical signals that govern scar healing, infarct expansion, aneurysm formation, or ventricular remodeling can be identified, they can be modified. Therefore, one major goal of our work on mechanics of healing infarcts is to provide a better understanding of the evolution of scar structure and mechanics as a platform for designing and appropriately applying therapies to improve ventricular function and to prevent infarct expansion, aneurysm formation, and adverse left ventricular remodeling. Considerable evidence also suggests that the interaction between healing infarcts and the surrounding myocardium works in the other direction: mechanical stimuli applied to the infarct by the myocardium can direct the development of infarct structure and mechanical properties. In particular, our work under the initial funding period of this project (12/01/03 – 11/30/07) revealed a striking correlation between scar structural and mechanical anisotropy in different animal models and the deformation patterns experienced by healing infarcts in those models. We hypothesize that mechanical environment governs the development of anisotropy in healing infarcts and represents a potentially important therapeutic target for directing infarct healing to optimize ventricular function and help prevent long-term adverse remodeling. The work proposed here will test this hypothesis using a combination of unique in vitro model systems and a new innovative approach to manipulating the mechanical environment of healing myocardial infarcts in vivo.

心肌梗死后，愈合瘢痕的机械性能是一个关键因素， 左心室功能、梗死扩展、动脉瘤形成和破裂的决定因素，以及 心室重构直到最近，解决这些问题的唯一治疗方案 结果是药理学的。然而，在过去的几年里， 改变心脏力学环境的选择从根本上改变了我们的 临床梗死后治疗的选择。在体心脏动态力学环境 现在，它和激素受体或信号级联一样，是一个有效的潜在治疗靶点。 原则上，如果控制瘢痕愈合、梗塞扩展、动脉瘤 形成，或心室重塑可以识别，他们可以修改。因此，一 我们在梗塞愈合机制方面的工作的主要目标是更好地理解 疤痕结构和力学的演变作为设计和适当的平台， 应用治疗以改善心室功能并防止梗塞扩大、动脉瘤 形成和不利的左心室重构。大量证据还表明， 在另一种情况下，正在愈合的梗死和周围心肌之间的相互作用起作用， 方向：心肌对梗塞部位施加的机械刺激可以引导心肌的运动。 梗死区结构和力学性能的发展。特别是，我们在 该项目的初步供资期（2003年1月12日至2007年11月30日）显示， 不同动物模型瘢痕结构和力学各向异性及变形 在这些模型中通过愈合梗塞所经历的模式。我们假设， 环境控制着各向异性的发展，并代表了一个 潜在的重要治疗靶点，用于指导梗死愈合以优化心室 功能和帮助防止长期不良重塑。这里提出的工作将检验这一点 使用独特的体外模型系统和一种新的创新的 方法来操纵机械环境愈合心肌梗死在体内。