title: Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization.
abstract: To investigate the role of secreted protein acidic and rich in cysteine (SPARC) in age-related cardiac inflammation, we studied six groups of mice: young (3-5 mo old), middle-aged (10-12 mo old), and old (18-29 mo old) C57BL/6 wild-type (WT) and SPARC-null (Null) mice (n = 7-10/group). Cardiac function and structure were determined by echocardiography. The left ventricle was used for cytokine gene array and macrophage quantification by immunohistochemistry. Macrophage infiltration increased with age in WT (n = 5-6/group, P < 0.05 for young vs. old), but not in Null. Proinflammatory markers (Ccl5, Cx3cl1, Ccr2, and Cxcr3) increased in middle-aged and old WT, whereas they were increased only in old Null compared with respective young (n = 5-6/group, P < 0.05 for all). These results suggest that SPARC deletion delayed age-related cardiac inflammation. To further assess how SPARC affects inflammation, we stimulated peritoneal macrophages with SPARC (n = 4). SPARC treatment increased expression of proinflammatory macrophage M1 markers and decreased anti-inflammatory M2 markers. Echocardiography (n = 7-10/group) revealed an age-related increase in wall thickness of the left ventricle in WT (0.76 ± 0.02 mm in young vs. 0.91 ± 0.03 mm in old; P < 0.05) but not in Null (0.78 ± 0.01 mm in young vs. 0.84 ± 0.02 mm in old). In conclusion, SPARC deletion delayed age-related increases in macrophage infiltration and proinflammatory cytokine expression in vivo and in vitro. SPARC acts as an important mediator of age-related cardiac inflammation by increasing the expression of macrophage M1 markers and decreasing M2 markers.
authors: Mississippi Center for Heart Research and San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan;
authors: Hiroe
authors: H
authors: Toba
authors: Mississippi Center for Heart Research and San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; Department of Physiology, East Carolina University, Greenville, North Carolina;
authors: Lisandra E
authors: LE
authors: de Castro Brás
authors: Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina;
authors: Catalin F
authors: CF
authors: Baicu
authors: Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, and.
authors: Michael R
authors: MR
authors: Zile
authors: Mississippi Center for Heart Research and San Antonio Cardiovascular Proteomics Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi; G. V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi.
authors: Merry L
authors: ML
authors: Lindsey
authors: Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, and bradshad@musc.edu.
authors: Amy D
authors: AD
authors: Bradshaw
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015676:Osteonectin / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: C503460:Ccl5 protein, mouse; C515335:Ccr2 protein, mouse; D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C515188:Cxcr3 protein, mouse; D018836:Inflammation Mediators; D015676:Osteonectin; D012333:RNA, Messenger; D054390:Receptors, CCR2; D054367:Receptors, CXCR3; C578250:SPARC protein, mouse
keywords: aging; heart; inflammation; macrophage; secreted protein acidic and rich in cysteine