Graham H K, Horn M, Trafford A W
Unit of Cardiac Physiology, University of Manchester, Manchester, UK.
Acta Physiol (Oxf). 2008 Sep;194(1):3-21. doi: 10.1111/j.1748-1716.2008.01881.x. Epub 2008 Jun 28.
The myocardial extracellular matrix (ECM), which preserves the geometry and integrity of the myocardium, is a dynamic structure whose component proteins are maintained by a finely controlled homeostatic balance between deposition and degradation. One of the key targets in cardiology is the elucidation of the molecular mechanisms which mediate pathological remodelling of this matrix causing the transition from compensatory hypertrophy to congestive decompensated heart failure. In response to injury or increased workload, cardiac remodelling including myocyte hypertrophy, develops as the heart attempts to compensate for increased wall stresses. Persistence of these stresses over extended time periods leads to disruption of ECM homeostasis resulting in irreversible maladaptive cardiac remodelling, ventricular dilatation and finally heart failure. ECM remodelling is regulated by the matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs). Clinical studies and experimental models of cardiac disease states have reported alterations in the balance between the MMPs and TIMPs in the failing heart and crucially at intermediate time points in the progression to failure. This article reviews the recent clinical, genetic and experimental approaches employed to compare ECM, MMP and TIMP profiles in healthy, compensated and failing hearts and identifies common themes in the perturbation of ECM homeostasis in the transition to heart failure.
心肌细胞外基质（ECM）维持着心肌的几何形状和完整性，是一种动态结构，其组成蛋白通过沉积和降解之间精细调控的稳态平衡得以维持。心脏病学的关键目标之一是阐明介导这种基质病理重塑的分子机制，这种重塑会导致从代偿性肥大转变为充血性失代偿心力衰竭。作为对损伤或工作量增加的反应，包括心肌细胞肥大在内的心脏重塑会在心脏试图补偿增加的壁应力时发生。这些应力在较长时间内持续存在会导致ECM稳态破坏，从而导致不可逆的适应性不良心脏重塑、心室扩张，最终导致心力衰竭。ECM重塑受基质金属蛋白酶（MMPs）及其内源性抑制剂（TIMPs）调节。心脏病状态的临床研究和实验模型报告了在衰竭心脏中以及在向衰竭进展的关键中间时间点，MMPs和TIMPs之间平衡的改变。本文综述了最近用于比较健康、代偿和衰竭心脏中ECM、MMP和TIMP谱的临床、遗传和实验方法，并确定了向心力衰竭转变过程中ECM稳态扰动的共同主题。
