Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction
This study tested the hypothesis that MMP-9(−/−)tPA(−/−) double knock out (i.e., MT(DKO)) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MT(DKO) mouse. Animals were categorized into sham-operated controls in MT(DKO) anima...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503422/ https://www.ncbi.nlm.nih.gov/pubmed/32867392 http://dx.doi.org/10.3390/ijms21176219 |
_version_ | 1783584390552485888 |
---|---|
author | Sung, Pei-Hsun Lin, Kun-Chen Chai, Han-Tan Chiang, John Y. Shao, Pei-Lin Luo, Chi-Wen Yip, Hon-Kan |
author_facet | Sung, Pei-Hsun Lin, Kun-Chen Chai, Han-Tan Chiang, John Y. Shao, Pei-Lin Luo, Chi-Wen Yip, Hon-Kan |
author_sort | Sung, Pei-Hsun |
collection | PubMed |
description | This study tested the hypothesis that MMP-9(−/−)tPA(−/−) double knock out (i.e., MT(DKO)) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MT(DKO) mouse. Animals were categorized into sham-operated controls in MT(DKO) animals (group 1) and in wild type (B6: group 2), AMI-MT(DKO) (group 3) and AMI-B6 (group 4) animals. They were euthanized, and the ischemic myocardium was harvested, by day 60 post AMI. The mortality rate was significantly higher in group 3 than in other groups and significantly higher in group 4 than in groups 1/2, but it showed no difference in the latter two groups (all p < 0.01). By day 28, the left-ventricular (LV) ejection fraction displayed an opposite pattern, whereas by day 60, the gross anatomic infarct size displayed an identical pattern of mortality among the four groups (all p < 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p < 0.01). The protein expressions of apoptosis (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP), fibrosis (Smad3/T-GF-ß), oxidative stress (NOX-1/NOX-2/oxidized-protein), inflammation (MMPs(2,9)/TNF-α/p-NF-κB), heart failure/pressure overload (BNP/ß-MHC) and mitochondrial/DNA damage (cytosolic-cytochrome-C/γ-H2AX) biomarkers displayed identical patterns, whereas the angiogenesis markers (small vessel number/CD31+cells in LV myocardium) displayed opposite patterns of mortality among the groups (all p < 0.0001). The microscopic findings of fibrotic/collagen deposition/infarct areas and inflammatory cell infiltration of LV myocardium were similar to the mortality among the four groups (all p < 0.0001). MT(DKO) strongly predicted unfavorable prognostic outcome after AMI. |
format | Online Article Text |
id | pubmed-7503422 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75034222020-09-23 Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction Sung, Pei-Hsun Lin, Kun-Chen Chai, Han-Tan Chiang, John Y. Shao, Pei-Lin Luo, Chi-Wen Yip, Hon-Kan Int J Mol Sci Article This study tested the hypothesis that MMP-9(−/−)tPA(−/−) double knock out (i.e., MT(DKO)) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MT(DKO) mouse. Animals were categorized into sham-operated controls in MT(DKO) animals (group 1) and in wild type (B6: group 2), AMI-MT(DKO) (group 3) and AMI-B6 (group 4) animals. They were euthanized, and the ischemic myocardium was harvested, by day 60 post AMI. The mortality rate was significantly higher in group 3 than in other groups and significantly higher in group 4 than in groups 1/2, but it showed no difference in the latter two groups (all p < 0.01). By day 28, the left-ventricular (LV) ejection fraction displayed an opposite pattern, whereas by day 60, the gross anatomic infarct size displayed an identical pattern of mortality among the four groups (all p < 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p < 0.01). The protein expressions of apoptosis (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP), fibrosis (Smad3/T-GF-ß), oxidative stress (NOX-1/NOX-2/oxidized-protein), inflammation (MMPs(2,9)/TNF-α/p-NF-κB), heart failure/pressure overload (BNP/ß-MHC) and mitochondrial/DNA damage (cytosolic-cytochrome-C/γ-H2AX) biomarkers displayed identical patterns, whereas the angiogenesis markers (small vessel number/CD31+cells in LV myocardium) displayed opposite patterns of mortality among the groups (all p < 0.0001). The microscopic findings of fibrotic/collagen deposition/infarct areas and inflammatory cell infiltration of LV myocardium were similar to the mortality among the four groups (all p < 0.0001). MT(DKO) strongly predicted unfavorable prognostic outcome after AMI. MDPI 2020-08-27 /pmc/articles/PMC7503422/ /pubmed/32867392 http://dx.doi.org/10.3390/ijms21176219 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sung, Pei-Hsun Lin, Kun-Chen Chai, Han-Tan Chiang, John Y. Shao, Pei-Lin Luo, Chi-Wen Yip, Hon-Kan Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title | Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title_full | Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title_fullStr | Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title_full_unstemmed | Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title_short | Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction |
title_sort | losing regulation of the extracellular matrix is strongly predictive of unfavorable prognostic outcome after acute myocardial infarction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503422/ https://www.ncbi.nlm.nih.gov/pubmed/32867392 http://dx.doi.org/10.3390/ijms21176219 |
work_keys_str_mv | AT sungpeihsun losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT linkunchen losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT chaihantan losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT chiangjohny losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT shaopeilin losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT luochiwen losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction AT yiphonkan losingregulationoftheextracellularmatrixisstronglypredictiveofunfavorableprognosticoutcomeafteracutemyocardialinfarction |