Age and SPARC change the extracellular matrix composition of the left ventricle

Lisandra E. De Castro Brás, Hiroe Toba, Catalin F. Baicu, Michael R. Zile, Susan T. Weintraub, Merry L. Lindsey, Amy D. Bradshaw

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23 Scopus citations

Abstract

Secreted protein acidic and rich in cysteine (SPARC), a collagen-binding matricellular protein, has been implicated in procollagen processing and deposition. The aim of this study was to investigate age- and SPARC-dependent changes in protein composition of the cardiac extracellular matrix (ECM). We studied 6 groups of mice (n = 4 /group): young (4-5 months old), middle-aged (11-12 m.o.), and old (18-29 m.o.) C57BL/6J wild type (WT) and SPARC null. The left ventricle (LV) was decellularized to enrich for ECM proteins. Protein extracts were separated by SDS-PAGE, digested in-gel, and analyzed by HPLC-ESI-MS/MS. Relative quantification was performed by spectral counting, and changes in specific proteins were validated by immunoblotting. We identified 321 proteins, of which 44 proteins were extracellular proteins. Of these proteins, collagen III levels were lower in the old null mice compared to WT, suggestive of a role for SPARC in collagen deposition. Additionally, fibrillin showed a significant increase in the null middle-aged group, suggestive of increased microfibril deposition in the absence of SPARC. Collagen VI increased with age in both genotypes (>3-fold), while collagen IV showed increased age-associated levels only in the WT animals (4-fold, P < 0.05). These changes may explain the previously reported age-associated increases in LV stiffness. In summary, our data suggest SPARC is a possible therapeutic target for aging induced LV dysfunction.

Original languageEnglish (US)
Article number810562
JournalBioMed Research International
Volume2014
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    De Castro Brás, L. E., Toba, H., Baicu, C. F., Zile, M. R., Weintraub, S. T., Lindsey, M. L., & Bradshaw, A. D. (2014). Age and SPARC change the extracellular matrix composition of the left ventricle. BioMed Research International, 2014, [810562]. https://doi.org/10.1155/2014/810562