Extracellular matrix (ECM) remodeling occurs in response to various cardiac insults including infarction, pressure overload and dilated myopathies. Each type of remodeling necessitates distinct types of ECM turnover and deposition yet an increase in myocardial fibrillar collagen content is appreciated as a contributing feature to cardiac dysfunction in each of these pathologies. In addition, aging, is also associated with increases in cardiac collagen content. The importance of characterizing differences in ECM composition and processes used by cardiac fibroblasts in the assembly of fibrotic collagen accumulation is critical for the design of strategies to reduce and ultimately regress cardiac fibrosis. Collagen cross-linking is one factor that influences collagen deposition and insolubility with direct implications for tissue properties such as stiffness. In this review, three different types of collagen cross-links shown to be important in cardiac fibrosis will be discussed; those catalyzed by lysyl oxidases, those catalyzed by transglutaminases, and those that result from non-enzymatic modification by the addition of advanced glycation end products. Insight into cellular mechanisms that govern collagen cross-linking in the myocardium will provide novel pathways for exploring new treatments to treat diseases associated with cardiac fibrosis.

细胞外基质（ECM）重塑是对各种心脏损伤的反应，包括梗塞、压力超负荷和扩张性肌病。每种类型的重塑都需要不同类型的 ECM 更新和沉积，但心肌原纤维胶原含量的增加被认为是每种病理中导致心脏功能障碍的一个促成特征。此外，衰老也与心脏胶原蛋白含量的增加有关。表征心脏成纤维细胞在纤维化胶原积累组装中使用的 ECM 成分和过程的差异的重要性对于设计减少并最终逆转心脏纤维化的策略至关重要。胶原交联是影响胶原沉积和不溶性的因素之一，对组织特性（例如硬度）有直接影响。在这篇综述中，将讨论三种不同类型的胶原交联，它们被证明对心脏纤维化很重要；由赖氨酰氧化酶催化的那些、由转谷氨酰胺酶催化的那些以及通过添加高级糖基化终产物而由非酶促修饰产生的那些。深入了解控制心肌中胶原蛋白交联的细胞机制将为探索治疗与心脏纤维化相关疾病的新疗法提供新途径。