Age and SPARC dependent cardiac collagen changes (1120.7)

Abstract

Secreted protein acidic and rich in cysteine (SPARC), a collagen‐binding matricellular protein, has been implicated in procollagen processing. The aim of this study was to investigate age and SPARC dependent changes in cardiac extracellular matrix (ECM). We studied 6 groups of mice (n=4/group): young (4‐5 month old), middle‐aged (11‐12 m.o.), and old (18‐23 m.o.) C57BL/6J wild type and SPARC‐null mice. The left ventricle was decellularized in 1% SDS with protease inhibitors in PBS to enrich for ECM proteins. Protein extracts (10 μg) were separated by SDS‐PAGE, digested in‐gel and analyzed by HPLC‐ESI‐MS/MS. Relative quantification was by spectral counting (Scaffold). We identified 321 proteins, of which 27 proteins were ECM or ECM‐related proteins. Of these proteins, 16 showed age‐dependent changes. Collagens I, III, IV and VI, dystrophin, and laminin b2 increased with age, which may explain previously reported age‐associated increases in cardiac stiffness. SPARC deletion blunted the age changes observed in collagens I and III and laminin b2. Of interest, fibrillin and elastin showed a significant increase with age in the Null mice, suggestive of increased microfibril deposition in the absence of SPARC. In summary, our data suggest SPARC is a possible therapeutic target for aging induced cardiac dysfunction.Grant Funding Source: Supported by HHSN 268201000036C (N01‐HV‐00244), R01 HL075360, HL051971, 1SC2 HL101430, 5I01BX000505