MICROSCOPIC CARDIAC MATERIAL PROPERTIES IN AGING

描述（改编自申请人摘要）：本提案的目标是 为了量化老化对人体三维结构的影响， 心室细胞外基质和心肌细胞在细胞水平上， 实验动物与disatolic功能障碍。申请人提议 阐明异常心脏结构的动态后果， 组合物，伴随着老化过程，通过测量固有的微观 材料特性，如质量密度、弹性和粘度， 与局部心肌功能相关。此外，申请人 将定义相关病理共病条件的作用， 糖尿病和高血压对间质结构的影响 可能在舒张功能恶化中起作用的基质成分 功能障碍新的气相色谱质谱法将用于测量 指示蛋白质交联的高级糖基化终产物 与测量材料属性的相关性。申请人建议 展示新型超声和磁共振成像的实用性 用于表征心脏纤维结构、材料性质和 运动，并为这些方法的临床应用细化范例。 他们将进一步量化潜在的回归或改善， 细胞外基质重塑在这些病理条件下， 血管紧张素转换酶抑制剂的药物治疗， 蛋白质交联的抑制剂，例如可能影响组织的氨基胍 基体组织组成和/或材料性能。的意义 拟议的研究在于阐明衰老对 基于组织材料表征的雌激素细胞基质重塑 在细胞水平上的属性和组织，这将决定性地 回答基本粘弹性刚度系数是否 老年人和年轻人的心脏微结构不同，如果 也就是细胞机制。

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.