STIFFNESS IN HYPERTROPHY-ROLE OF CARDIOCYTE CYTOSKELETON

描述(改编自申请人的摘要)：申请人 假设心肌细胞外基质(ECM) 而心肌细胞(心肌细胞)负责这些变化 舒张期充血性心力衰竭时的舒张期功能 (瑞士法郎)。某些形式的心肌肥厚时细胞外基质的变化 会导致舒张期功能的显著改变，但心脏功能异常 舒张期功能不能用细胞外基质的变化来解释 独自一人。申请人称，首席调查员的研究 表明心脏细胞本身的变化使一个主要的、独立的 在心肌舒张性功能障碍的发生和发展中的作用 舒张期充血性心力衰竭然而，无论是绝对贡献还是相对贡献， 心肌细胞组成特性的主要变化导致这些 舒张期功能异常已被明确界定。这个 申请人表示，有关心肌细胞在心脏中的作用的问题 舒张性充血性心力衰竭的发展尚未完全得到解答：1)是心肌细胞 松弛速度、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引起这些 心脏功能的改变？以及3)在蜂窝中进行这些改变， 心脏细胞水平的变化是由心脏引起的。 心肌，心脏组织水平？研究将在心肌细胞中进行 以及从正常猫、右室猫分离的乳头肌 压力超负荷性肥厚与猫右室 容量超负荷肥大。松弛、僵硬和粘度将是 在基线状态下检查，然后在微管发生急性变化后进行检查 聚合反应。申请人认为初步数据表明：1) 压力超负荷性肥厚导致心肌松弛功能下降 速度，被动刚度增加，粘性阻尼力增加； 2)这些变化至少在一定程度上是由于 细胞骨架的微管部分；以及3)这些异常 心肌松弛功能下降与心脏功能的关系 心率、心肌硬度增加和心肌粘度增加 发生在压力超负荷肥厚时。

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.