title: The role of secreted protein acidic and rich in cysteine (SPARC) in cardiac repair and fibrosis: Does expression of SPARC by macrophages influence outcomes?
abstract: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular, collagen-binding protein. Matricellular proteins are described as extracellular matrix-associated proteins that do not serve classical structural roles in the matrix such as those ascribed to laminins and collagens. The family of matricellular proteins modulates cell:extracellular matrix interactions and is actively expressed during tissue remodeling. Functional activities attributed to SPARC in cultured cells include regulation of cell adhesion, cytoskeletal rearrangement, proliferation, and matrix assembly. The primary phenotype characteristic of SPARC-null mice is a deficit in amounts of fibrillar collagen and fibril morphology. Strikingly, SPARC-null mice demonstrate a blunted fibrotic response in a number of different tissue settings. The role of monocyte/macrophages as an important component of tissue fibrosis is becoming increasingly appreciated. Expression of SPARC by bone marrow derived inflammatory cells raises the interesting proposition that SPARC produced by infiltrating leukocytes might contribute to the course of inflammation and tissue fibrosis in the heart. This review will summarize results from studies defining the function of SPARC in myocardial repair and fibrosis and results from other non-cardiac tissues that shed light onto possible consequences of SPARC expression by monocyte/macrophages in the setting of heart disease.
authors.affiliation: Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, MSC 773, Charleston, SC 29425, United States; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, United States. Electronic address: bradshad@musc.edu.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Bradshaw
mesh_terms: D000367:Age Factors; D000818:Animals; D001794:Blood Pressure; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D055595:Mechanical Phenomena; D040542:Mechanotransduction, Cellular; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009205:Myocarditis / Q000209:etiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D015676:Osteonectin; C577241:SPARC protein, human
keywords: BM40; Collagen; Extracellular matrix; Inflammation; Matricellular; Osteonectin