Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.
BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3130031?pdf=render |
| _version_ | 1818313632526630912 |
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| author | Mikihiko Arikawa Yoshihiko Kakinuma Takemi Handa Fumiyasu Yamasaki Takayuki Sato |
| author_facet | Mikihiko Arikawa Yoshihiko Kakinuma Takemi Handa Fumiyasu Yamasaki Takayuki Sato |
| author_sort | Mikihiko Arikawa |
| collection | DOAJ |
| description | BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI. |
| first_indexed | 2024-12-13T08:36:50Z |
| format | Article |
| id | doaj.art-28286cb0737840f696c0d2b5958c6689 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T08:36:50Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-28286cb0737840f696c0d2b5958c66892022-12-21T23:53:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2062910.1371/journal.pone.0020629Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.Mikihiko ArikawaYoshihiko KakinumaTakemi HandaFumiyasu YamasakiTakayuki SatoBACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.http://europepmc.org/articles/PMC3130031?pdf=render |
| spellingShingle | Mikihiko Arikawa Yoshihiko Kakinuma Takemi Handa Fumiyasu Yamasaki Takayuki Sato Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. PLoS ONE |
| title | Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. |
| title_full | Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. |
| title_fullStr | Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. |
| title_full_unstemmed | Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. |
| title_short | Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice. |
| title_sort | donepezil anti alzheimer s disease drug prevents cardiac rupture during acute phase of myocardial infarction in mice |
| url | http://europepmc.org/articles/PMC3130031?pdf=render |
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