| First Author | McCurdy SM | Year | 2011 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 301 |
| Issue | 2 | Pages | H497-505 |
| PubMed ID | 21602472 | Mgi Jnum | J:173342 |
| Mgi Id | MGI:5013883 | Doi | 10.1152/ajpheart.01070.2010 |
| Citation | McCurdy SM, et al. (2011) SPARC mediates early extracellular matrix remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol 301(2):H497-505 |
| abstractText | 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 mul (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 +/- 3 to 63 +/- 5 mul; 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. |
