HYPERTROPHY OF CULTURED SHR CARDIAC MYOCYTE

培养的 SHR 心肌细胞肥大

• 批准号: 3349684
• 负责人: WILLIAM C CLAYCOMB
• 金额: $ 13.96万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349684
• 关键词: animal age group; biochemistry; biological models; cardiovascular disorder prevention; enzyme substrate; gene expression; genetic transcription; heart cell; hydralazine; hypertension; isozymes; molecular pathology; ventricular hypertrophy

Our objectives are to determine if primary cultures of cardiac muscle cells from normal and hypertrophied hearts retain their patterns of substrate preference, adrenergic responsiveness, myosin isozyme transcription and translation and morphological characteristics and to determine if hypertrophy of the left ventricle of the spontaneously hypertensive rat (SHR) is due to a genetic defect in the heart muscle cell per se, represents an adaptive response to the systemic hypertension or is a consequence of both of these factors. In order to accomplish these objectives we will isolate and culture cardiac muscle cells from the adult SHR rat and determine if they retain in culture certain biochemical and morphological characteristics observed in the intact animal and in perfused hearts from SHR rats. A multidisciplinary approach will be taken in that both metabolic and morphological studies are planned. Several drugs will be used to dissociate the cardiac hypertrophy from the systemic hypertension, and myocardial cells cultured from these animals will also be characterized. We also plan to culture cardiac muscle cells from neonatal SHR rats to determine if they will develop "SHR-Characteristics" in culture. These experiments should allow us to determine if the hypertrophy is a consequence of the level and duration of hypertension or is an intrinsic genetic defect in the muscle cell. Studies of cultured cardiac muscle cells from hearts of normal and hypertensive rats should allow us to better define the specific defects which are responsible for this condition and may allow us to develop a model of the adult hypertrophied cardiac muscle cell in culture. Such an in vitro model would provide a system to more precisely determine what factors are responsible for enlargement of the heart muscle cell and the molecular mechanisms involved.

我们的目标是确定原代培养的心肌细胞 正常和肥大的心脏保留了它们的基质模式 偏好，肾上腺素能反应，肌球蛋白同工酶转录和 翻译和形态特征，并确定是否 自发性高血压大鼠左心室肥厚 (SHR)是由于心肌细胞本身的遗传缺陷， 代表对全身性高血压的适应性反应，或者是 这两个因素的后果。 为了完成这些 目的分离培养成人心肌细胞， SHR大鼠，并确定他们是否保留在培养某些生化和 在完整动物和灌注动物中观察到的形态学特征 SHR大鼠的心脏。 将采取多学科办法， 计划进行代谢和形态学研究。 几种药物将 用于将心脏肥大与全身性肥大分离开来 高血压，从这些动物中培养的心肌细胞也将被 表征了 我们还计划从新生儿中培养心肌细胞 SHR大鼠，以确定他们是否会发展“SHR特征”， 文化 这些实验可以让我们确定 是高血压水平和持续时间的结果，或者是 肌肉细胞的内在遗传缺陷。 培养心肌的研究 正常和高血压大鼠心脏的肌肉细胞应该可以让我们 更好地定义导致这种情况的具体缺陷 并可能使我们能够建立一个成人肥大心脏的模型， 培养的肌肉细胞。 这种体外模型将提供一种系统， 更准确地确定是什么因素导致了 心肌细胞和相关的分子机制。