STIFFNESS IN HYPERTROPHY-ROLE OF CARDIOCYTE CYTOSKELETON

描述（改编自申请人摘要）：申请人 假设心肌细胞外基质（ECM） 和心肌细胞（心肌细胞）负责的变化， 舒张期充血性心力衰竭时出现舒张功能 （瑞士法郎）。 在某些形式的心肌肥大中发生的ECM变化 可引起舒张功能的显著变化，但 不能根据ECM的变化来解释舒张功能 一个人 申请人声明，主要研究者的研究 表明心肌细胞本身的变化是一个主要的，独立的， 导致心肌舒张功能障碍的发生， 舒张期CHF。 然而，无论是绝对还是相对贡献， 心肌细胞组成特性的主要变化使这些 舒张功能的异常已经被清楚地定义。 的 申请人指出，关于心肌细胞在心肌细胞中的作用的问题， 舒张期CHF的发展尚未得到充分回答：1）心肌细胞 松弛率、硬度或粘度因疾病过程而改变， 引起舒张期充血性心力衰竭？ 2)是什么细胞结构或过程导致这些 心肌细胞功能的改变 3）这些变化发生在细胞上， 心肌细胞水平的原因有助于发生的变化， 心肌，心脏组织水平？ 研究将在心肌细胞中进行 和乳头肌分离正常猫，猫右心室 压力超负荷性心肌肥厚与右心室肥厚猫 容量超负荷肥大 松弛度、硬度和粘度将 在基线状态下检查，然后在微管发生急性变化后， 聚合法 申请人认为初步数据表明：1） 压力超负荷肥大导致心肌细胞松弛减少 速率，被动刚度的增加，以及粘性阻尼的增加; 2)这些变化至少部分是由于 微管部分的细胞骨架;和3）这些异常， 心肌细胞功能的下降有助于心肌舒张 心率、心肌硬度增加和心肌粘度增加 这发生在压力超负荷肥大期间。

DESCRIPTION (adapted from the applicant's abstract): The applicant hypothesizes that changes in both the myocardial extracellular matrix (ECM) and the cardiac muscle cell (cardiocyte) are responsible for the changes in diastolic function which occur during diastolic congestive heart failure (CHF). Changes in the ECM which occur in some forms of cardiac hypertrophy can cause significant changes in diastolic function, but abnormalities in diastolic function cannot be explained on the basis of changes in the ECM alone. The applicant states that studies by the principal investigator suggest that changes in the cardiocyte itself make a major, independent contribution to the development of myocardial diastolic dysfunction and diastolic CHF. However, neither the absolute nor relative contribution that primary changes in cardiocyte constitutive properties make to these abnormalities in diastolic function have been clearly defined. The applicant indicates that questions about the role of the cardiocyte in the development of diastolic CHF have not been fully answered: 1) Is cardiocyte relaxation rate, stiffness, or viscosity changed by disease processes which cause diastolic CHF? 2) What cellular structures or processes cause these change in cardiocyte function? And 3) Do these changes at the cellular, cardiocyte level contribute causally to the changes which occur at the myocardial, cardiac tissue level? Studies will be performed in cardiocytes and papillary muscles isolated from normal cats, cats with right ventricular pressure-overload hypertrophy and cats with right ventricular volume-overload hypertrophy. Relaxation, stiffness, and viscosity will be examined in the baseline state and then after an acute change in microtubule polymerization. The applicant believes preliminary data suggest that: 1) pressure overload hypertrophy causes a decrease in cardiocyte relaxation rate, an increase in passive stiffness, and an increase in viscous damping; 2) these changes are caused, at least in part, by an increase in the microtubule portion of the cytoskeleton; and 3) these abnormalities in cardiocyte function contribute to the decrease in myocardial relaxation rate, increase in myocardial stiffness, and increase in myocardial viscosity which occur during pressure overload hypertrophy.