SPARC Facilitates Inflammation in the Aging Heart and Suppresses Macrophage M2 Polarization

Abstract

Cardiac aging is characterized by inflammation and fibrosis. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to play a role in extracellular matrix assembly and inflammation. SPARC levels increase with age in the left ventricle. We hypothesized that SPARC might facilitate age‐related cardiac inflammation. We studied 6 groups of mice (n=7‐10/group): young (3‐5 month old), middle‐aged (10‐12 m.o.) and old (18‐29 m.o.) C57BL/6J wild type (WT) and SPARC‐null (Null). Left ventricular wall thickness and myocyte size increased in an age‐related manner in WT but not Null (both p<0.05). Expression of pro‐inflammatory markers (Ccl5, Cx3cl1, Ccr2, Cxcr3) and Adamts1were increased in middle‐aged and old WT and old Null compared to respective young (all p<0.05). Versican is a substrate of Adamts1 that when cleaved promotes cell infiltration, and it decreased with age only in WT (p<0.05). Expression of α2 integrin and macrophage infiltration were increased with age in WT, but not Null. Isolated peritoneal macrophages from young and old WT showed similar levels of pro‐inflammatory M1 markers (Ccl5, Ccl3, Tnfα); however, peritoneal macrophages from old WT mice displayed reduced anti‐inflammatory M2 markers (Arg1, Mrc1). SPARC treatment of young macrophages decreased M2 markers to levels observed in old mice. In summary, SPARC mediates age‐related cardiac inflammation by suppressing M2 macrophage polarization.