SPARC mediates early extracellular matrix remodeling following myocardial infarction

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 se...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2011-08, Vol.301 (2), p.H497-H505
Main Authors: McCurdy, Sarah M, Dai, Qiuxia, Zhang, Jianhua, Zamilpa, Rogelio, Ramirez, Trevi A, Dayah, Tariq, Nguyen, Nguyen, Jin, Yu-Fang, Bradshaw, Amy D, Lindsey, Merry L
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Blotting, Western
Cells
Disease Models, Animal
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Female
Fibroblasts - metabolism
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation
Heart attacks
Heart Rupture, Post-Infarction - metabolism
Heart Rupture, Post-Infarction - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Contraction
Myocardial Infarction - diagnostic imaging
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardial Infarction - physiopathology
Myocardium - metabolism
Myocardium - pathology
Oligonucleotide Array Sequence Analysis
Osteonectin - deficiency
Osteonectin - genetics
Osteonectin - metabolism
Physiology
Protein synthesis
Rodents
Signaling and Stress Response
Stroke Volume
Time Factors
Ultrasonography
Ventricular Function, Left
Ventricular Remodeling - genetics
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Summary: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.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.01070.2010