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...

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Autores principales: Sung, Pei-Hsun, Lin, Kun-Chen, Chai, Han-Tan, Chiang, John Y., Shao, Pei-Lin, Luo, Chi-Wen, Yip, Hon-Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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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
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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.
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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
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