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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/H2216    most recent 01343.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Mukherjee, R. Articles by Spinale, F. G. Search for Related Content PubMed PubMed Citation Articles by Mukherjee, R. Articles by Spinale, F. G.

Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction

¹Division of Cardiothoracic Surgery, Medical University of South Carolina, and ⁴Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina; ²McKnight Vision Research Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; and ³Department of Medicine, Veterans Affairs Medical Center/University of California, San Francisco, California

Submitted 20 December 2005 ; accepted in final form 5 June 2006

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 -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. -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.

structure; remodeling; matrix metalloproteinases

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