Myocardial Extracellular Matrix An Ever-Changing and Diverse Entity

nonstructural properties accommodating multiple proteins growth factor– cell receptor–binding properties. present review will describe in detail the central involvement of nonstructural proteins in cardiac development and cardiac remodeling. Our focus will mainly be on glycosylation, the decoration of proteins with added sugars that results in di-versification of protein functionality, creating proteoglycans and glycoproteins, the well-known matricellular proteins. 1,2 To the understanding of functional diversity that added sugars to cardiac ECM, describe some basic biochemical concepts regarding their Abstract: 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. ( Circ Res 2014;114:872-888.) Postulates Matrix Metalloproteinase Postmyocardial Infarction Remodeling: Cardiac Extracellular Matrix: Ever-Changing Diverse Entity Interstitial Transport System Perspectives degrade the ECM and releasing cytokines bound in the matrix. The degraded ECM elements may further amplify the immune response by either stimulating important danger signal receptors such as TLR­4 (eg, hyaluronan, decorin, and versican) or producing chemokine gradients for the recruitment of leukocytes (eg, syndecan). Furthermore, proteoglycans, such as decorin and biglycan, and glycoproteins, such as SPARC, enable proper collagen assembly. An independent role of glycosaminoglycans (CS, DS, and HS) is starting to emerge, further elaborating the extensive repertoire of the ECM in health and disease. CS indicates chondroitin sulfate; DS, dermatan sulfate; HS, heparan sulfate; KS, keratan sulfate; and TLR­4, toll­like receptor­4.