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MYOCARDIAL COLLAGEN GENE EXPRESSION--HORMONAL REGULATION

心肌胶原蛋白基因表达--激素调节

基本信息

批准号：
2735154
负责人：
Mahboubeh Eghbali-Webb
金额：
$ 14.27万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-01-01 至 1999-06-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) It is now well recognized that the remodeling of the fibrillar collagen matrix that occurs in ventricular hypertrophy may adversely alter myocardial stiffness and lead to heart failure. The investigators have established that in ventricular hypertrophy induced by hemodynamic and hormonal stimuli the remodeling of collagen matrix is linked to alterations in collagen gene expression. They discovered that in contrast to animal models of ventricular hypertrophy induced by abdominal aortic banding and infusion of hypertensive doses of norepinephrine, thyroid hormone induced ventricular hypertrophy is not associated with cardiac fibrosis and is characterized by decrease in collagen type I gene expression. In vitro studies have demonstrated that thyroid hormone induced inhibition of the activity of collagen type I promoter occurs in cardiac fibroblast and changes in the stability of collagen type I mRNA take place. The hypothesis is that the thyroid hormone induced inhibition of collagen type I gene expression in cardiac fibroblast is mediated by the interaction of thyroid hormone induced nuclear proteins with thyroid hormone response elements on collagen type I promoter and that the activator proteins (AP-1) participates in the negative regulation of collagen gene expression by thyroid hormones. The objective, therefore, is to identify the cis-acting elements and the trans-acting factors involved in thyroid hormone induced inhibition of collagen type I gene expression in cardiac fibroblast. The results are expected to help in elucidation of the thyroid hormone sensitive pathways involved in the remodeling of the heart collagen matrix in pathological conditions and during development and growth.

描述：（改编自研究者摘要）它现在很好我们认识到，在心室肥大中，可能不利地改变心肌硬度，心脏衰竭研究人员已经确定，在心室由血流动力学和激素刺激诱导的肥大，胶原基质与胶原基因表达的改变有关。他们发现与心室肥大的动物模型相比，通过腹主动脉结扎术和高血压剂量的去甲肾上腺素、甲状腺激素不诱发心室肥厚与心脏纤维化相关，其特征在于 I型胶原基因表达。体外研究表明，甲状腺激素诱导的I型胶原活性抑制启动子发生在心脏成纤维细胞和变化的稳定性， I型胶原mRNA的表达。假设是甲状腺激素诱导抑制心肌成纤维细胞I型胶原基因表达由甲状腺激素诱导的核蛋白相互作用介导在I型胶原启动子上具有甲状腺激素反应元件，激活蛋白（AP-1）参与了细胞凋亡的负调控，胶原基因表达的甲状腺激素。因此，我们的目标是以确定参与的顺式作用元件和反式作用因子，甲状腺激素诱导的I型胶原基因表达抑制心脏成纤维细胞这些结果有望有助于阐明甲状腺激素敏感通路参与心脏重塑病理条件下和发育过程中的胶原基质，增长