Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction
Open Access
- 1 November 2006
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 291 (5), H2216-H2228
- https://doi.org/10.1152/ajpheart.01343.2005
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.Keywords
This publication has 45 references indexed in Scilit:
- Gender differences in cardiac function during early remodeling after acute myocardial infarction in miceLife Sciences, 2004
- Myocardial hypertrophy of normotensive Wistar-Kyoto ratsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2004
- Influence of sex on ventricular remodeling after myocardial infarction in miceJournal of the American Society of Echocardiography, 2003
- A functional activating protein 1 (AP-1) site regulates matrix metalloproteinase 2 (MMP-2) transcription by cardiac cells through interactions with JunB-Fra1 and JunB-FosB heterodimersBiochemical Journal, 2003
- Integration of concepts: Cardiac extracellular matrix remodeling after myocardial infarctionJournal of Cardiac Failure, 2002
- Combinatorial Interactions of p53, Activating Protein-2, and YB-1 with a Single Enhancer Element Regulate Gelatinase A Expression in Neoplastic CellsPublished by Elsevier BV ,2002
- Effect of Ramipril and Furosemide Treatment on Interstitial Remodeling in Post-Infarction Heart Failure Rat HeartsJournal of Molecular and Cellular Cardiology, 2002
- Selective Matrix Metalloproteinase Inhibition Reduces Left Ventricular Remodeling but Does Not Inhibit Angiogenesis After Myocardial InfarctionCirculation, 2002
- Angiotensin Blockade Inhibits Increased JNKs, AP-1 and NF- κ B DNA-binding Activities in Myocardial Infarcted RatsJournal of Molecular and Cellular Cardiology, 2001
- Quantification of left ventricular volumes by two-dimensional echocardiography: a simplified and accurate approach.Circulation, 1983