Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction Article (Web of Science)

abstract

  • Myocardial remodeling after myocardial infarction (MI) is associated with increased levels of the matrix metalloproteinases (MMPs). Levels of two MMP species, MMP-2 and MMP-9, are increased after MI, and transgenic deletion of these MMPs attenuates post-MI left ventricular (LV) remodeling. This study characterized the spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 after MI. MI was induced in transgenic mice in which the MMP-2 or MMP-9 promoter sequence was fused to the β-galactosidase reporter, and reporter level was assayed up to 28 days after MI. Myocardial localization with respect to cellular sources of MMP-2 and MMP-9 promoter induction was examined. After MI, LV diameter increased by 70% ( P < 0.05), consistent with LV remodeling. β-Galactosidase staining in MMP-2 reporter mice was increased by 1 day after MI and increased further to 64 ± 6% of LV epicardial area by 7 days after MI ( P < 0.05). MMP-2 promoter activation occurred in fibroblasts and myofibroblasts in the MI region. In MMP-9 reporter mice, promoter induction was detected after 3 days and peaked at 7 days after MI (53 ± 6%, P < 0.05) and was colocalized with inflammatory cells at the peri-infarct region. Although MMP-2 promoter activation was similarly distributed in the MI and border regions, activation of the MMP-9 promoter was highest at the border between the MI and remote regions. These unique findings visually demonstrated that activation of the MMP-2 and MMP-9 gene promoters occurs in a distinct spatial relation with reference to the MI region and changes in a characteristic time-dependent manner after MI.

authors

  • Mukherjee, Rupak
  • Mingoia, Joseph T.
  • Bruce, James A.
  • Austin, Jeffrey S.
  • Stroud, Robert E.
  • Escobar, G. Patricia
  • McClister, David M.
  • Allen, Claire M.
  • Alfonso-Jaume, Maria Alejandra
  • Fini, M. Elizabeth
  • Lovett, David H.
  • Spinale, Francis G.

publication date

  • 2006

start page

  • H2216

end page

  • H2228

volume

  • 291

issue

  • 5