PMID- 20863528 OWN - NLM STAT- MEDLINE DCOM- 20120214 LR - 20211020 IS - 1095-8673 (Electronic) IS - 0022-4804 (Print) IS - 0022-4804 (Linking) VI - 172 IP - 1 DP - 2012 Jan TI - Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction. PG - 59-67 LID - 10.1016/j.jss.2010.06.015 [doi] AB - BACKGROUND: Left ventricular (LV) remodeling following myocardial infarction (MI) is associated with increased levels of specific matrix metalloproteinases (MMPs) and relative reduction of endogenous tissue inhibitors of the MMPs (TIMPs). However, transcriptional mechanisms for the disparate post-MI MMP/TIMP expression remain unknown. Using murine constructs designed to report gene promoter activation, this study tested the hypothesis that distinctly different temporal profiles of MMP-2, MMP-9, and TIMP-1 transcription occurs post-MI. METHODS/RESULTS: Transcriptional activity (beta-galactosidase (beta-gal) reporter constructs) of MMP-2 (n = 49), MMP-9 (n = 62), or TIMP-1 (n = 40) was assayed at 1 h (acute), and 1-28 d after MI (coronary ligation) in transgenic reporter mice. At 7 d post-MI, the area of promoter activation normalized to LV area was increased from acute values for MMP-2 (63.4 +/- 5.8 versus 1.1% +/- 1.0%, P < 0.05) and MMP-9 (53.1 +/- 6.1 versus 1.3% +/- 0.9%, P < 0.05). While TIMP-1 promoter activation at 7 d post-MI increased from acute values (3.6 +/- 1.3 versus 0.3% +/- 0.5%, P < 0.05), this increase was smaller than that for MMP-2 or MMP-9 (both P < 0.05). MMP-2 promoter activation peaked in the MI region at 7 d post-MI and MMP-9 promoter activation was highest in the border region at 7 and 14 d post-MI. TIMP-1 promoter activation peaked within the MI region at 7 d post-MI and within the remote region at 14 d post-MI. CONCLUSIONS: These findings provided direct in vivo evidence that discordant changes in temporal and spatial patterns of MMP/TIMP transcription occurs with MI. Restoration of TIMP-1 promoter activation may represent a molecular therapeutic target to attenuate/prevent adverse post-MI LV remodeling. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Mukherjee, Rupak AU - Mukherjee R AD - Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. mukherr@musc.edu FAU - Snipes, Jonathan M AU - Snipes JM FAU - Saunders, Stuart M AU - Saunders SM FAU - Zavadzkas, Juozas A AU - Zavadzkas JA FAU - Spinale, Francis G AU - Spinale FG LA - eng GR - P01-HL48788/HL/NHLBI NIH HHS/United States GR - HL-97012/HL/NHLBI NIH HHS/United States GR - R03 HL097012/HL/NHLBI NIH HHS/United States GR - R01 HL066029/HL/NHLBI NIH HHS/United States GR - R01 HL066029-04/HL/NHLBI NIH HHS/United States GR - P01 HL048788-150006/HL/NHLBI NIH HHS/United States GR - P01 HL048788/HL/NHLBI NIH HHS/United States GR - HL-66029/HL/NHLBI NIH HHS/United States GR - R01 HL059165-08/HL/NHLBI NIH HHS/United States GR - M01 RR001070/RR/NCRR NIH HHS/United States GR - HL-45024/HL/NHLBI NIH HHS/United States GR - M01 RR001070-290350/RR/NCRR NIH HHS/United States GR - R01 HL059165/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100702 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - EC 3.2.1.23 (beta-Galactosidase) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Coronary Vessels/physiopathology MH - Disease Models, Animal MH - Female MH - Ligation MH - Male MH - Matrix Metalloproteinase 2/genetics/*metabolism MH - Matrix Metalloproteinase 9/genetics/*metabolism MH - Mice MH - Mice, Transgenic MH - Myocardial Infarction/*metabolism/pathology/physiopathology MH - Myocardium/metabolism/pathology MH - Promoter Regions, Genetic/genetics/*physiology MH - Tissue Inhibitor of Metalloproteinase-1/genetics/*metabolism MH - Ventricular Remodeling MH - beta-Galactosidase/metabolism PMC - PMC3010347 MID - NIHMS213925 EDAT- 2010/09/25 06:00 MHDA- 2012/02/15 06:00 PMCR- 2013/01/01 CRDT- 2010/09/25 06:00 PHST- 2010/01/29 00:00 [received] PHST- 2010/05/10 00:00 [revised] PHST- 2010/06/08 00:00 [accepted] PHST- 2010/09/25 06:00 [entrez] PHST- 2010/09/25 06:00 [pubmed] PHST- 2012/02/15 06:00 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - S0022-4804(10)00557-3 [pii] AID - 10.1016/j.jss.2010.06.015 [doi] PST - ppublish SO - J Surg Res. 2012 Jan;172(1):59-67. doi: 10.1016/j.jss.2010.06.015. Epub 2010 Jul 2.