Department of Physiology, James H Quillen College of Medicine, James H Quillen Veterans Affairs Medical Center, East Tennessee State University, PO Box 70576, Johnson City, TN 37614, USA.
J Mol Cell Cardiol. 2010 Mar;48(3):538-43. doi: 10.1016/j.yjmcc.2009.06.015. Epub 2009 Jun 30.
Remodeling after myocardial infarction (MI) associates with left ventricular (LV) dilation, decreased cardiac function and increased mortality. The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play a significant role in myocardial remodeling post-MI. Expression of osteopontin (OPN) increases in the heart post-MI. Evidence has been provided that lack of OPN induces LV dilation which associates with decreased collagen synthesis and deposition. Inhibition of matrix metalloproteinases, key players in ECM remodeling process post-MI, increased ECM deposition (fibrosis) and improved LV function in mice lacking OPN after MI. This review summarizes--1) signaling pathways leading to increased expression of OPN in the heart; 2) the alterations in the structure and function of the heart post-MI in mice lacking OPN; and 3) mechanisms involved in OPN-mediated ECM remodeling post-MI.
心肌梗死后（MI）的重构与左心室（LV）扩张、心功能降低和死亡率增加有关。细胞外基质（ECM）蛋白的动态合成和分解在 MI 后心肌重构中起着重要作用。MI 后心脏中骨桥蛋白（OPN）的表达增加。有证据表明，OPN 的缺乏会导致 LV 扩张，这与胶原合成和沉积减少有关。MI 后缺乏 OPN 的小鼠中，基质金属蛋白酶（ECM 重塑过程中的关键因子）的抑制增加了 ECM 的沉积（纤维化），改善了 LV 功能。这篇综述总结了：1）导致心脏中 OPN 表达增加的信号通路；2）MI 后缺乏 OPN 的小鼠心脏结构和功能的改变；3）MI 后 OPN 介导的 ECM 重塑涉及的机制。
