{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:06:47Z","timestamp":1790467607605,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study tested the hypothesis that MMP-9\u2212\/\u2212tPA\u2212\/\u2212 double knock out (i.e., MTDKO) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MTDKO mouse. Animals were categorized into sham-operated controls in MTDKO animals (group 1) and in wild type (B6: group 2), AMI-MTDKO (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 &lt; 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 &lt; 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p &lt; 0.01). The protein expressions of apoptosis (mitochondrial-Bax\/cleaved-caspase3\/cleaved-PARP), fibrosis (Smad3\/T-GF-\u00df), oxidative stress (NOX-1\/NOX-2\/oxidized-protein), inflammation (MMPs2,9\/TNF-\u03b1\/p-NF-\u03baB), heart failure\/pressure overload (BNP\/\u00df-MHC) and mitochondrial\/DNA damage (cytosolic-cytochrome-C\/\u03b3-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 &lt; 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 &lt; 0.0001). MTDKO strongly predicted unfavorable prognostic outcome after AMI.<\/jats:p>","DOI":"10.3390\/ijms21176219","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T09:17:08Z","timestamp":1598606228000},"page":"6219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-9752","authenticated-orcid":false,"given":"Pei-Hsun","family":"Sung","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Tan","family":"Chai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-4017","authenticated-orcid":false,"given":"John Y.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung 804201, Taiwan"},{"name":"Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Nursing, Asia University, Taichung 413, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-575X","authenticated-orcid":false,"given":"Chi-Wen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"},{"name":"Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-5717","authenticated-orcid":false,"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Nursing, Asia University, Taichung 413, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1083\/jcb.201101100","article-title":"The cell biology of disease: Cellular mechanisms of cardiomyopathy","volume":"194","author":"Harvey","year":"2011","journal-title":"J. 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