Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice
Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusi...
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/7174127 |
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| author | Georg D. Duerr Daniela Dewald Eva J. Schmitz Luise Verfuerth Katharina Keppel Christine Peigney Alexander Ghanem Armin Welz Oliver Dewald |
| author_facet | Georg D. Duerr Daniela Dewald Eva J. Schmitz Luise Verfuerth Katharina Keppel Christine Peigney Alexander Ghanem Armin Welz Oliver Dewald |
| author_sort | Georg D. Duerr |
| collection | DOAJ |
| description | Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT-/-)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. |
| format | Article |
| id | doaj-art-e3e605f8526840d8a85b41428881000f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-e3e605f8526840d8a85b41428881000f2025-02-03T05:53:41ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/71741277174127Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in MiceGeorg D. Duerr0Daniela Dewald1Eva J. Schmitz2Luise Verfuerth3Katharina Keppel4Christine Peigney5Alexander Ghanem6Armin Welz7Oliver Dewald8Department of Cardiac Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Anesthesiology, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Ophthalmology, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Cardiac Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of General, Visceral, Thoracic and Vascular Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Cardiac Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Medicine II-Cardiology, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Cardiac Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Cardiac Surgery, University Clinical Center, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyAims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT-/-)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT-/--hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2-/--hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT-/--hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2-/--hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.http://dx.doi.org/10.1155/2016/7174127 |
| spellingShingle | Georg D. Duerr Daniela Dewald Eva J. Schmitz Luise Verfuerth Katharina Keppel Christine Peigney Alexander Ghanem Armin Welz Oliver Dewald Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice Mediators of Inflammation |
| title | Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice |
| title_full | Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice |
| title_fullStr | Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice |
| title_full_unstemmed | Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice |
| title_short | Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice |
| title_sort | metallothioneins 1 and 2 modulate inflammation and support remodeling in ischemic cardiomyopathy in mice |
| url | http://dx.doi.org/10.1155/2016/7174127 |
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