In vivo matrix metalloproteinase-7 substrates identified in the left ventricle post-myocardial infarction using proteomics

Ying Ann Chiao, Rogelio Zamilpa, Elizabeth F. Lopez, Qiuxia Dai, Gladys P. Escobar, Kevin Hakala, Susan T. Weintraub, Merry L. Lindsey

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Matrix metalloproteinase-7 (MMP-7) deletion has been shown to improve survival after myocardial infarction (MI). MMP-7 has a large array of in vitro substrates, but in vivo substrates for MMP-7 following MI have not been fully identified. Accordingly, we evaluated the infarct regions of wild-type (WT; n = 12) and MMP-7 null (null; n = 10) mice using a proteomic strategy. Seven days post-MI, infarct regions of the left ventricles were excised, homogenized, and protein extracts were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Of 13 spots that showed intensity differences between WT and null, the intensities of eight spots were higher and those of five spots were lower in the null group (p < 0.05). Fibronectin and tenascin-C, known in vitro substrates of MMP-7, were identified in spots that showed lower intensity in the null. Immunoblotting and in vitro cleavage assays confirmed reduced fibronectin and tenascin-C fragment generation in the null, and this effect was restored by exogenous administration of MMP-7. Lower levels of full-length peroxiredoxin-1 and -2 and higher levels of the full-length peroxiredoxin-3 were detected in the null group, suggesting MMP-7 deletion may also indirectly regulate protein levels through nonenzymatic mechanisms. In conclusion, this is the first study to identify fibronectin and tenascin-C as in vivo MMP-7 substrates in the infarcted left ventricle using a proteomic approach.

Original languageEnglish (US)
Pages (from-to)2649-2657
Number of pages9
JournalJournal of proteome research
Volume9
Issue number5
DOIs
StatePublished - May 7 2010

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Matrix Metalloproteinase 7
Proteomics
Heart Ventricles
Myocardial Infarction
Substrates
Tenascin
Fibronectins
Peroxiredoxins
Peroxiredoxin III
Electrophoresis, Gel, Two-Dimensional
Electrophoresis
Immunoblotting
Mass spectrometry
Assays
Mass Spectrometry
Proteins
Gels

Keywords

  • Cardiac remodeling
  • MMP-7
  • Mice
  • Myocardial infarction
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

In vivo matrix metalloproteinase-7 substrates identified in the left ventricle post-myocardial infarction using proteomics. / Chiao, Ying Ann; Zamilpa, Rogelio; Lopez, Elizabeth F.; Dai, Qiuxia; Escobar, Gladys P.; Hakala, Kevin; Weintraub, Susan T.; Lindsey, Merry L.

In: Journal of proteome research, Vol. 9, No. 5, 07.05.2010, p. 2649-2657.

Research output: Contribution to journalArticle

Chiao, Ying Ann ; Zamilpa, Rogelio ; Lopez, Elizabeth F. ; Dai, Qiuxia ; Escobar, Gladys P. ; Hakala, Kevin ; Weintraub, Susan T. ; Lindsey, Merry L. / In vivo matrix metalloproteinase-7 substrates identified in the left ventricle post-myocardial infarction using proteomics. In: Journal of proteome research. 2010 ; Vol. 9, No. 5. pp. 2649-2657.
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