MOLECULAR AND CELLULAR BIOLOGY OF CARDIAC INTERSTITIUM

心肌由三个部分组成：肌肉、血管系统和 间质。作为胶原周转的一部分的吸收和重塑， 包括组织对纤维状胶原的初始降解 胶原酶。正常或病理状态下的胶原蛋白堆积 可由胶原合成增强或抑制所致 胶原蛋白溶解机制。在自然生长和各种疾病中 与心肌肥大生长相关的状态和 令人印象深刻的心脏间质结构重建是显而易见的。 到目前为止，人们对胶原酶的作用知之甚少。 正常和肥厚心脏间质重塑的研究 心肌。这个项目的总体目标是研究 胶原酶基因在心肌中的表达及其与胶原酶的连接 心脏胶原基质重塑的基因调控。 为此，我们将研究：胶原酶基因在 正常心肌与胶原酶基因转录调控 转录后水平通过测量转录后水平 和翻译后水平通过 左心室压力超负荷时的酶活性测定 肥大。我们还将研究转型的监管效果。 生长因子-β对心肌细胞胶原酶基因表达的影响 文化。

The myocardium consists of three compartments: muscle, vasculature; and interstitium. Resorption and remodeling as part of collagen turnover, involves an initial degradation of fibrillar collagen by tissue collagenases. Accumulation of collagen in normal or pathological states can result from either enhanced collagen synthesis or inhibited collagenolytic mechanism. During natural growth and in various disease states associated with hypertrophic growth of the myocardium an impressive structural remodeling of the cardiac interstitium is evident. To date little is known about the contribution of collagenase to the remodeling of the cardiac interstitium in the normal and hypertrophied myocardium. The overall objective of this project is to study collagenase gene expression in the myocardium and to link collagenase gene regulation to the remodeling of the collagen matrix in the heart. Toward this end we will examine: collagenase gene expression in the normal myocardium and collagenase gene regulation at transcriptional level by nuclear run-on assay; post-transcriptional level by measurement of steady state levels of mRNA; and post-translational level by measurement of enzyme activity in left ventricular pressure overload hypertrophy. We will also examine the regulatory effects of transforming growth factor-beta on collagenase gene expression in cardiac cell culture.