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.
Highlights
Age is a prominent risk factor for increased cardiovascular morbidity and mortality, and the incidence of cardiovascular diseases such as hypertension and myocardial infarction (MI) are higher in individuals over 65 years of age [1]
To further study the impact of this matricellular protein in cardiac extracellular matrix (ECM) and aging, we developed an enrichment protocol coupled with a proteomic approach to analyze Secreted protein acidic and rich in cysteine (SPARC) and age-dependent changes in the expression and accumulation of cardiac ECM proteins
We identified 321 proteins by mass spectrometry, of which 44 proteins (13.7%) were extracellular, including secreted and cell membrane proteins (Figure 1)
Summary
Age is a prominent risk factor for increased cardiovascular morbidity and mortality, and the incidence of cardiovascular diseases such as hypertension and myocardial infarction (MI) are higher in individuals over 65 years of age [1]. Aging has been associated with significant structural changes in the left ventricle (LV) and data from several clinical trials show evidence that elderly patients have poorer outcomes after ischemic stress [2, 3]. The age-related decline in function of the cardiovascular system is associated with myocyte loss and a subsequent increase in the cardiac extracellular matrix (ECM) [4,5,6]. Evolving evidence suggests that cardiac senescence by itself affects myocardial structure and function that can affect how one responds to additional cardiac stressors. The frequent presence of comorbidities has hindered the identification of cardiac age-related therapeutic targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
