Matricellular Proteins in Myocardial Infarction

Peter      Huebener; Nikolaos   G.   Frangogiannis

Abstract

Matricellular proteins are extracellular matrix proteins that do not play a direct structural role but act contextually modulating cell function and activity. These structurally diverse proteins include Thrombospondin (TSP)-1 and -2, tenascin-C and -X, Osteonectin/SPARC (Secreted protein, acidic and rich in cysteine) and osteopontin (OPN). Matricellular proteins show low level expression in normal adult tissues, but are markedly upregulated in wound healing and tissue remodeling. Our review examines our current knowledge of the expression and role of the matricellular proteins in the infarcted heart. TSP-1 and tenascin-C are upregulated in the border zone of healing infarcts. TSP-1 null mice exhibit enhanced and prolonged inflammation and extension of the inflammatory infiltrate into the non-infarcted areas, suggesting a role for TSP-1 in containment of the inflammatory response. These defects are probably due to impaired TGF-β activation and lead to increased adverse remodeling. OPN is markedly upregulated in healing infarcts and is predominantly localized in a subset of macrophages. OPN -/- mice show increased left ventricular dilation and defective collagen deposition in the infarct. SPARC is also markedly induced in experimental models of infarction; however, its role in the healing process remains unknown. Matricellular proteins play an important role in the orchestration of the molecular events involved in infarct healing by modulating a wide range of cellular responses. Understanding the role of specific functional domains of the matricellular proteins in infarct healing may result in identification of novel therapeutic strategies aiming at optimizing cardiac repair.

Keywords: myocardium, Tenascin-C, Remodeling, Cardiac Injury, Thrombospondins, OSTEOPONTIN