Year: 2014
Type: article
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.
Source: BioMed Research International
DOI: 10.1155/2014/810562
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,680
Funders: U.S. Department of Veterans Affairs, American Heart Association, Office of Research and Development, National Institutes of Health, University of Texas Health Science Center at San Antonio, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences
Awards: G1336385654, G2501379408, G2522261593, G2532004172, Systems Biology of Macrophage Polarizaiton Following Myocardial Infarction, G2790983157, G2962370141, G4086130786, G4336994553, G4386296807, G4737602250, G5286880059, Cardiovascular Dynamics & Their Control, G6408202313, G6480796884, G7204903766, G7480745220, G752354275, Cardiorenal and Metabolic Diseases Research Center, G8047249856, Protective effects of cilnidipine against hyperuricemia-related renal and vascular injury, G8767263632, G9000115909
OpenAlex ID: W2046285259