Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.
Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment wi...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0192720 |
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| author | Kimberly Spaulding Kiyoaki Takaba Alexander Collins Farshid Faraji Guanying Wang Esteban Aguayo Liang Ge David Saloner Arthur W Wallace Anthony J Baker David H Lovett Mark B Ratcliffe |
| author_facet | Kimberly Spaulding Kiyoaki Takaba Alexander Collins Farshid Faraji Guanying Wang Esteban Aguayo Liang Ge David Saloner Arthur W Wallace Anthony J Baker David H Lovett Mark B Ratcliffe |
| author_sort | Kimberly Spaulding |
| collection | DOAJ |
| description | Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity. |
| format | Article |
| id | doaj-art-56f8bd079baf4cbf975c5ead44a216f4 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-56f8bd079baf4cbf975c5ead44a216f42025-08-20T02:36:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01132e019272010.1371/journal.pone.0192720Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.Kimberly SpauldingKiyoaki TakabaAlexander CollinsFarshid FarajiGuanying WangEsteban AguayoLiang GeDavid SalonerArthur W WallaceAnthony J BakerDavid H LovettMark B RatcliffeDecreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.https://doi.org/10.1371/journal.pone.0192720 |
| spellingShingle | Kimberly Spaulding Kiyoaki Takaba Alexander Collins Farshid Faraji Guanying Wang Esteban Aguayo Liang Ge David Saloner Arthur W Wallace Anthony J Baker David H Lovett Mark B Ratcliffe Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. PLoS ONE |
| title | Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. |
| title_full | Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. |
| title_fullStr | Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. |
| title_full_unstemmed | Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. |
| title_short | Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. |
| title_sort | short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility |
| url | https://doi.org/10.1371/journal.pone.0192720 |
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