Controlling myocardial matrix remodeling: implications for heart failure.
Controlling myocardial matrix remodeling: implications for heart failure.
复制标题
控制心肌基质重塑：对心力衰竭的影响。
DOI：
10.1097/00045415-199905000-00010
复制
发表时间：
1999
影响因子：
2.1
通讯作者：
Spinale,FG
中科院分区：
文献类型：
--
作者：
Rao,VU;Spinale,FG
进行性充血性心力衰竭（CHF）通常伴有左心室几何形状和心肌结构的改变，通常称为心肌重塑。已经观察到心肌的胶原基质内发生重要变化，可能有助于重塑过程。心肌胶原基质受两个基本过程的影响：胶原合成和胶原降解。基质金属蛋白酶是参与基质降解的锌依赖性酶的内源性家族，并且已被证明由一类称为金属蛋白酶组织抑制剂的蛋白质调节。一些研究已经确定了心肌基质金属蛋白酶和金属蛋白酶组织抑制剂表达的变化与CHF的发展。这些观察结果导致了一种假设，即金属蛋白酶活性增加和金属蛋白酶组织抑制剂水平降低导致胶原蛋白重塑，破坏肌细胞排列并促进CHF左心室重塑过程。因此，开发能够调节心肌基质金属蛋白酶活性和表达的药物代表了一种新的和潜在的治疗CHF的重要靶点。
Progressive congestive heart failure (CHF) is often accompanied by a change in left ventricular geometry and myocardial architecture, commonly referred to as myocardial remodeling. It has been observed that important changes occur within the collagen matrix of the myocardium, potentially contributing to the remodeling process. The myocardial collagen matrix is influenced by 2 fundamental processes: collagen synthesis and collagen degradation. Matrix metalloproteinases are an endogenous family of zinc-dependent enzymes involved in matrix degradation and have been shown to be regulated by a class of proteins called the tissue inhibitors of metalloproteinases. Several studies have identified changes in myocardial matrix metalloproteinase and tissue inhibitors of metalloproteinase expression with the development of CHF. These observations have led to the hypothesis that increased metalloproteinase activity and decreased levels of tissue inhibitors of metalloproteinase result in collagen remodeling that disrupts myocyte alignment and facilitates the left ventricular remodeling process with CHF. Thus, the development of pharmacologic agents that will modulate the activity and expression of myocardial matrix metalloproteinases represents a new and potentially significant therapeutic target for developing CHF.