Introduction to Translational Cardiovascular Research by Dennis V. Cokkinos

Author:Dennis V. Cokkinos
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

16.3.6.2 The Role of the Matricellular Proteins

Matricellular proteins are a family of structurally unrelated macromolecules that do not play a structural role, but bind to the matrix and modulate cell-cell and cell-matrix interactions [72]. Temporally and spatially restricted induction and deposition of matricellular proteins is observed in the proliferative phase of infarct healing. Our laboratory has demonstrated that the matricellular protein thrombospondin (TSP)-1, a crucial TGF-β activator with potent angiostatic and anti-inflammatory properties, is strikingly upregulated in the border zone of the infarct [73]. TSP-1 null mice exhibited enhanced and prolonged expression of chemokines in the infarcted heart and showed expansion of the inflammatory infiltrate into the noninfarcted area. These findings suggest an important role for TSP-1 in suppression and containment of the inflammatory reaction following infarction. Therefore, localized induction of TSP-1 in the infarct border zone may form a “barrier” preventing expansion of the inflammatory infiltrate into the noninfarcted area. Other matricellular proteins, such as TSP-2, SPARC/osteonectin, osteopontin (OPN), tenascin-C and periostin are also upregulated in the infarcted heart and modulate the reparative response (Fig. 16.4) [72].

Fig. 16.4The matricellular proteins osteopontin, SPARC, tenascin-C, periostin and thrombospondin-1 regulate fibroblast phenotype and activity in the healing infarct. Other specialized matrix proteins (such as ED-A fibronectin) also play a critical role in myofibroblast conversion

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