| First Author | Toba H | Year | 2015 |
| Journal | Am J Physiol Cell Physiol | Volume | 308 |
| Issue | 12 | Pages | C972-82 |
| PubMed ID | 25877699 | Mgi Jnum | J:224697 |
| Mgi Id | MGI:5688800 | Doi | 10.1152/ajpcell.00402.2014 |
| Citation | Toba H, et al. (2015) Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization. Am J Physiol Cell Physiol 308(12):C972-82 |
| abstractText | 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. |
