From Maastricht University Medical Centre, Maastricht, The Netherlands.
Circ Res. 2014 Feb 28;114(5):872-88. doi: 10.1161/CIRCRESAHA.114.302533.
The cardiac extracellular matrix (ECM) is a complex architectural network consisting of structural and nonstructural proteins, creating strength and plasticity. The nonstructural compartment of the ECM houses a variety of proteins, which are vital for ECM plasticity, and can be divided into 3 major groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common denominator for these groups is glycosylation, which refers to the decoration of proteins or lipids with sugars. This review will discuss the fundamental role of the matrix in cardiac development, homeostasis, and remodeling, from a glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans, biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are upregulated on cardiac injury and regulate key processes in the remodeling myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some parallels can be made regarding the processes these proteins are involved in, their specific functions are extremely diverse. In fact, under varying conditions, individual proteins can even have opposing functions, making spatiotemporal contribution of these proteins in the rearrangement of multifaceted ECM very hard to grasp. Alterations of protein characteristics by the addition of sugars may explain the immense, yet tightly regulated, variability of the remodeling cardiac matrix. Understanding the role of glycosylation in altering the ultimate function of glycoproteins, proteoglycans, and glycosaminoglycans in the myocardium may lead to the development of new biochemical structures or compounds with great therapeutic potential for patients with heart disease.
心脏细胞外基质 (ECM) 是一种复杂的结构网络，由结构蛋白和非结构蛋白组成，为心脏提供强度和可塑性。ECM 的非结构性部分包含多种对 ECM 可塑性至关重要的蛋白质，可以分为 3 大主要类别：糖蛋白、蛋白聚糖和糖胺聚糖。这些类别都有一个共同点，即糖基化，这是指在蛋白质或脂质上添加糖。从糖生物学的角度来看，本篇综述将讨论基质在心脏发育、稳态和重塑中的基本作用。糖蛋白（例如，血小板反应蛋白、富含半胱氨酸的酸性分泌蛋白、腱糖蛋白）、蛋白聚糖（例如，神经黏蛋白、 syndecans、 biglycan）和糖胺聚糖（例如，透明质酸、硫酸乙酰肝素）在心脏损伤时上调，并调节重塑心肌中的关键过程，如炎症、纤维化和血管生成。尽管这些蛋白质参与的过程有一些相似之处，但它们的具体功能却极其多样化。事实上，在不同的条件下，单个蛋白质甚至可能具有相反的功能，这使得这些蛋白质在复杂 ECM 的重新排列中的时空贡献很难把握。糖的添加改变了蛋白质的特性，这可能解释了重塑心脏基质的巨大但又受到严格调控的变异性。了解糖基化在改变糖蛋白、蛋白聚糖和糖胺聚糖在心肌中的最终功能方面的作用，可能为心脏病患者开发具有巨大治疗潜力的新型生化结构或化合物提供思路。
