SPARC mediates early extracellular matrix remodeling following myocardial infarction

Sarah M. McCurdy, Qiuxia Dai, Jianhua Zhang, Rogelio Zamilpa, Trevi A. Ramirez, Tariq Dayah, Nguyen Nguyen, Yu Fang Jin, Amy D. Bradshaw, Merry L. Lindsey

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 enddiastolic volumes from 45 ± 2 to 83 ± 5 ±l (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 ± 3 to 63 ± 5 ±l; 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. cardiac fibroblasts; left ventricular remodeling; mice; secreted protein, acidic, and rich in cysteine.

Original languageEnglish (US)
Pages (from-to)H497-H505
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 1 2011

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Extracellular Matrix
Cysteine
Myocardial Infarction
Proteins
Fibroblasts
Tissue Inhibitor of Metalloproteinase-2
Matrix Metalloproteinase 3
Fibronectins
Heart Ventricles
Collagen
Connective Tissue Growth Factor
Gene Expression
Ventricular Remodeling
Tissue Extracts
Matrix Metalloproteinase Inhibitors
Cicatrix
Echocardiography
Wounds and Injuries
Genes

Keywords

  • Acidic
  • Cardiac fibroblasts
  • Left ventricular remodeling
  • Mice
  • Rich in cysteine
  • Secreted protein

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

SPARC mediates early extracellular matrix remodeling following myocardial infarction. / 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.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 2, 01.08.2011, p. H497-H505.

Research output: Contribution to journalArticle

McCurdy, SM, Dai, Q, Zhang, J, Zamilpa, R, Ramirez, TA, Dayah, T, Nguyen, N, Jin, YF, Bradshaw, AD & Lindsey, ML 2011, 'SPARC mediates early extracellular matrix remodeling following myocardial infarction', American Journal of Physiology - Heart and Circulatory Physiology, vol. 301, no. 2, pp. H497-H505. https://doi.org/10.1152/ajpheart.01070.2010
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. / SPARC mediates early extracellular matrix remodeling following myocardial infarction. In: American Journal of Physiology - Heart and Circulatory Physiology. 2011 ; Vol. 301, No. 2. pp. H497-H505.
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