After induced myocardial infarction in transgenic mice, MMP-2 and MMP-9 promoter induction peaked at 7 days (64 +/- 6% and 53 +/- 6% of LV epicardial area, respectively; P<0.05).
Does myocardial infarction induce distinct spatiotemporal patterns of MMP-2 and MMP-9 promoter activation in transgenic mice?
The study demonstrates that MMP-2 and MMP-9 gene promoters are activated in distinct spatial and temporal patterns following myocardial infarction, providing insight into the cellular mechanisms of post-MI left ventricular remodeling.
p-value: p=<0.05
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 beta-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. beta-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.
Mukherjee et al. (Sat,) conducted a other in Myocardial infarction. Myocardial infarction induction was evaluated on Spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 (beta-galactosidase reporter level) (p=<0.05). After induced myocardial infarction in transgenic mice, MMP-2 and MMP-9 promoter induction peaked at 7 days (64 +/- 6% and 53 +/- 6% of LV epicardial area, respectively; P<0.05).
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