MICROSCOPIC CARDIAC MATERIAL PROPERTIES IN AGING

描述(改编自申请者摘要)：本提案的目标是 为了量化衰老对人脑三维结构的影响 心肌细胞水平上的心肌细胞外基质和心肌细胞 心功能不全的实验动物。申请者建议 阐明心脏结构异常的动态后果和 通过测量内部微观结构来测量伴随老化过程的成分 材料特性，如质量密度、弹性和粘度，这将 与局部心肌功能相关。此外，申请人 将定义相关的病理并存条件的作用，如 糖尿病和高血压对间质特异性结构改变的影响 基质成分在舒张期心肌梗死中的作用 功能障碍。将使用新的气相色谱-质谱仪方法来测量 指示蛋白质直接交联的糖基化终末产物 与测量材料特性的相关性。申请人建议： 展示新型超声和磁共振成像技术的实用性 表征心肌纤维结构、材料特性和性能的方法 运动，并勾勒出这些方法的临床应用范例。 他们将进一步量化潜在的回归或改善 这些病理条件下的细胞外基质重塑 血管紧张素转换酶抑制剂和血管紧张素转换酶的药物治疗 蛋白质交联的抑制剂，例如可能影响组织的氨基胍 基质组织组成和/或材料特性。的重要意义。 这项拟议的研究旨在阐明衰老对健康的影响 基于组织材料特性的去细胞基质重塑 属性和组织，这最终将 回答基本粘弹性刚度系数是否 心脏微结构在衰老和年轻心脏之间的不同，如果 那么哪种细胞机制。

DESCRIPTION (Adapted from Applicant's Abstract): The goal of this proposal is to quantify the effects of aging on the three dimensional architecture of the ventricular extracellular matrix and myocytes at the cellular level in experimental animals with disatolic dysfunction. The applicants proposed to elucidate the dynamic consequences of abnormal cardiac architecture and composition that accompany the aging process by measuring intrinsic microscopic material properties such as mass density, elasticity and viscosity, which will be correlated with regional myocardial function. In addition, the applicant would define the role of associated pathological comorbid condision such as diabetes and hypertension on specific strucutrla alterations of interstitial matrix components that may play a role in the exacerbation of diastolic dysfunction. New gas chromatography mass spec methods would be used to measure advance glycation end products indicative of protein crosslinking for direct correlation with measure material properties. The applicant proposed to demonstrate the utility of novel ultrasound and magnetic resonance imaging methods for characterizing cardiac fiber architecture, material properties and motion, and deliniate paradigms for clinical applications of these methods. They would further quantify potential regression or improvemten of extracellular matrix remodeling under these pathologic conditions a pharmacologic therapy with angiotensisn converting enxyme inhibitors and inhibitors of protein crosslinking e.g. amino guanidine which may affect tissue matrix orgaization composition and or material properites. The significance of the proposed research resides in elucidation of the effects of aging on estracellular matrix remodeling, based on characterization of tissue material properties and organization at the cellular level, which will definitively answer the question of whether fundamental visco elastic stiffness coefficients of the cardiac microarchitecture differ between aging and young hearts, and if so which cellular mechanisms.