Age and SPARC change the extracellular matrix composition of the left ventricle.
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.
Mississippi Center for Heart Research, University of Mississippi Medical Center (UMMC), Jackson, MS 39216, USA ; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio (UTHSCA), San Antonio, TX 78229, USA.
Lisandra E
LE
de Castro Brás
Mississippi Center for Heart Research, University of Mississippi Medical Center (UMMC), Jackson, MS 39216, USA ; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio (UTHSCA), San Antonio, TX 78229, USA ; Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan.
Hiroe
H
Toba
Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Catalin F
CF
Baicu
Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA ; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29401, USA.
Michael R
MR
Zile
San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio (UTHSCA), San Antonio, TX 78229, USA ; Department of Biochemistry, UTHSCSA, San Antonio, TX 78229, USA.
Susan T
ST
Weintraub
Mississippi Center for Heart Research, University of Mississippi Medical Center (UMMC), Jackson, MS 39216, USA ; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio (UTHSCA), San Antonio, TX 78229, USA ; Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA.
Merry L
ML
Lindsey
Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA ; Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC 29401, USA.
Amy D
AD
Bradshaw
D000375:Aging / Q000378:metabolism*; D000818:Animals; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D051379:Mice; D015676:Osteonectin / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
D024061:Collagen Type III; D024141:Collagen Type IV; D015676:Osteonectin; C578250:SPARC protein, mouse