Lin C-S, Pan C-H
Department of Biological Science and Technology, National Chiao Tung University, No. 75 Po-Ai Street, Hsinchu, Taiwan.
Cell Mol Life Sci. 2008 May;65(10):1489-508. doi: 10.1007/s00018-008-7408-8.
Electrical, contractile and structural remodeling have been characterized in atrial fibrillation (AF), and the latter is considered to be the major contributor to AF persistence. Recent data show that interstitial fibrosis can predispose to atrial conduction impairment and AF induction. The interplay between cardiac matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs), is thought to be critical in atrial extracellular matrix (ECM) metabolism. At the molecular level, angiotensin II, transforming growth factor-beta1, inflammation and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodeling in AF. Therefore, we review recent advances in the understanding of the atrial fibrotic process, the major downstream components in this remodeling process, and the expression and regulation of MMPs and TIMPs. We also describe the activation of bioactive molecules in both clinical studies and animal models to modulate MMPs and TIMPs and their effects on atrial fibrosis in AF.
在心房颤动（AF）中，电重构、收缩功能重构和结构重构均有其特征表现，而后者被认为是房颤持续存在的主要原因。近期数据表明，间质纤维化易导致心房传导障碍及房颤诱发。心脏基质金属蛋白酶（MMPs）与其内源性抑制剂基质金属蛋白酶组织抑制剂（TIMPs）之间的相互作用，被认为在心房细胞外基质（ECM）代谢中起关键作用。在分子水平上，血管紧张素II、转化生长因子-β1、炎症和氧化应激对于房颤中ECM失调和心房纤维化重构尤为重要。因此，我们综述了在心房纤维化过程的理解、该重构过程中的主要下游成分以及MMPs和TIMPs的表达与调控方面的最新进展。我们还描述了在临床研究和动物模型中生物活性分子的激活对MMPs和TIMPs的调节作用及其对房颤中心房纤维化的影响。
