From the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (A.-H.L., P.P.L.); University of Toronto, Heart & Stroke/Lewar Centre of Excellence, Toronto, Ontario, Canada (P.P.L.); University of California, San Diego, School of Medicine (F.J.V., R.A.G.); and Bristol-Myers Squibb Company, Pennington, NJ (R.A.G.).
Circ Res. 2014 Feb 28;114(5):916-27. doi: 10.1161/CIRCRESAHA.114.302819.
The cardiac extracellular matrix (ECM) provides the architectural scaffold to support efficient contraction and relaxation of cardiomyocytes. The elegant design of the ECM facilitates optimal force transduction, electric transmission, intercellular communication, and metabolic exchange within the myocardial microenvironment. In the setting of increased wall stress, injury, or disease, the ECM can undergo a series of dynamic changes that lead to favorable chamber remodeling and functional adaptation. Over time, sustained matrix remodeling can impair diastolic and systolic function caused by excess deposition of interstitial fibrous tissue. These pathological alterations in ECM structure/function are considered central to the evolution of adverse cardiac remodeling and the development of heart failure. This review discusses the complex dynamics of the cardiac ECM in the setting of myocardial infarction, pressure overload, and volume overload. We also summarize the current status of ECM biomarkers that may have clinical value in prognosticating cardiac disease progression in patients. Finally, we discuss the most current status of drugs under evaluation for use in cardiac fibrosis.
心脏细胞外基质（ECM）为心肌细胞的高效收缩和舒张提供了结构支架。ECM 的精巧设计促进了心肌微环境内最佳的力转导、电传递、细胞间通讯和代谢交换。在壁面应力增加、损伤或疾病的情况下，ECM 可经历一系列动态变化，导致有利的心室重构和功能适应。随着时间的推移，基质持续重塑会导致细胞间质纤维组织过度沉积，从而损害舒张和收缩功能。这些 ECM 结构/功能的病理性改变被认为是导致不良心脏重构和心力衰竭发展的核心因素。本综述讨论了心肌梗死、压力超负荷和容量超负荷情况下心脏 ECM 的复杂动力学。我们还总结了 ECM 生物标志物的现状，这些标志物可能对预测患者心脏疾病进展具有临床价值。最后，我们讨论了目前正在评估用于治疗心脏纤维化的药物的最新状况。
