title: SPARC mediates early extracellular matrix remodeling following myocardial infarction.
abstract: Secreted protein, acidic, and rich in cysteine (SPARC) is a matricellular protein that functions in the extracellular processing of newly synthesized collagen. Collagen deposition to form a scar is a key event following a myocardial infarction (MI). Because the roles of SPARC in the early post-MI setting have not been defined, we examined age-matched wild-type (WT; n=22) and SPARC-deficient (null; n=25) mice at day 3 post-MI. Day 0 WT (n=28) and null (n=20) mice served as controls. Infarct size was 52 ± 2% for WT and 47 ± 2% for SPARC null (P=NS), indicating that the MI injury was comparable in the two groups. By echocardiography, WT mice increased end-diastolic volumes from 45 ± 2 to 83 ± 5 μl (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 ± 3 to 63 ± 5 μl; P < 0.05 vs. day 0 controls and vs. WT day 3 MI). Ejection fraction fell post-MI in WT mice from 57 ± 2 to 19 ± 1%. The decrease in ejection fraction was attenuated in the absence of SPARC (65 ± 2 to 28 ± 2%). Fibroblasts isolated from SPARC null left ventricle (LV) showed differences in the expression of 22 genes encoding extracellular matrix and adhesion molecule genes, including fibronectin, connective tissue growth factor (CTGF; CCN2), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-2 (TIMP-2). The change in fibroblast gene expression levels was mirrored in tissue protein extracts for fibronectin, CTGF, and MMP-3 but not TIMP-2. Combined, the results of this study indicate that SPARC deletion preserves LV function at day 3 post-MI but may be detrimental for the long-term response due to impaired fibroblast activation.
authors: Cardiology Division, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors: Sarah M
authors: SM
authors: McCurdy
authors: Qiuxia
authors: Q
authors: Dai
authors: Jianhua
authors: J
authors: Zhang
authors: Rogelio
authors: R
authors: Zamilpa
authors: Trevi A
authors: TA
authors: Ramirez
authors: Tariq
authors: T
authors: Dayah
authors: Nguyen
authors: N
authors: Nguyen
authors: Yu-Fang
authors: YF
authors: Jin
authors: Amy D
authors: AD
authors: Bradshaw
authors: Merry L
authors: ML
authors: Lindsey
references: Dev Dyn. 2004 Aug;230(4):787-94
references: 15254913
references: Exp Mol Pathol. 2009 Feb;86(1):23-31
references: 19094982
references: Circulation. 2009 Jan 20;119(2):269-80
references: 19118257
references: J Proteome Res. 2010 May 7;9(5):2649-57
references: 20232908
references: J Cell Biochem. 2011 Apr;112(4):1003-8
references: 21308731
references: J Exp Med. 2009 Jan 16;206(1):113-23
references: 19103879
references: Proteomics. 2010 Jun;10(11):2214-23
references: 20354994
references: J Biol Chem. 1992 Feb 25;267(6):3581-4
references: 1371271
references: Hum Mol Genet. 2010 Oct 15;19(20):3895-905
references: 20639395
references: J Gerontol A Biol Sci Med Sci. 2000 Jan;55(1):B35-41; discussion B42-3
references: 10719761
references: J Biol Chem. 2007 Jul 27;282(30):22062-71
references: 17522057
references: J Clin Invest. 2001 May;107(9):1049-54
references: 11342565
references: Ann N Y Acad Sci. 2010 Feb;1188:143-52
references: 20201897
references: Int J Cardiol. 2010 Aug 6;143(1):20-8
references: 19195725
references: Am J Respir Cell Mol Biol. 2002 Aug;27(2):141-50
references: 12151305
references: Cardiovasc Res. 2009 Nov 1;84(2):273-82
references: 19542177
references: Cardiovasc Res. 2005 Feb 1;65(2):469-77
references: 15639486
references: J Proteome Res. 2008 Feb;7(2):756-65
references: 18166010
references: J Histochem Cytochem. 2010 Oct;58(10):871-9
references: 20566756
references: J Mol Cell Cardiol. 2010 Mar;48(3):544-9
references: 19577572