Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice
Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Result...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/9450439 |
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| author | Yangchen Dhondup Ivar Sjaastad Øystein Sandanger Jan Magnus Aronsen Muhammad Shakil Ahmed Håvard Attramadal Alexandra Vanessa Finsen Lili Zhang Trine Ranheim Katrine Alfsnes Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge |
| author_facet | Yangchen Dhondup Ivar Sjaastad Øystein Sandanger Jan Magnus Aronsen Muhammad Shakil Ahmed Håvard Attramadal Alexandra Vanessa Finsen Lili Zhang Trine Ranheim Katrine Alfsnes Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge |
| author_sort | Yangchen Dhondup |
| collection | DOAJ |
| description | Aim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced survival compared to SERC2a KO mice, with a median life expectancy of 58 days compared to 63 days. Both HF groups displayed increased left atrium size, lung weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis. However, there were no significant differences between the groups. Conclusion. In mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median life expectancy. The cause remains elusive, as all investigated HF parameters were unaltered. Still, these findings support a salutary role of TLR9 in some subsets of HF conditions and underline the importance for future studies on the mechanisms of TLR9 in diastolic HF. |
| format | Article |
| id | doaj-art-574432b69998439ab5a5f81e21132c63 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-574432b69998439ab5a5f81e21132c632025-02-03T01:31:06ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/94504399450439Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure MiceYangchen Dhondup0Ivar Sjaastad1Øystein Sandanger2Jan Magnus Aronsen3Muhammad Shakil Ahmed4Håvard Attramadal5Alexandra Vanessa Finsen6Lili Zhang7Trine Ranheim8Katrine Alfsnes9Pål Aukrust10Geir Christensen11Arne Yndestad12Leif Erik Vinge13Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayCenter for Heart Failure Research, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, Ullevaal, Oslo, NorwayK.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, NorwayK.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayCenter for Heart Failure Research, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayCenter for Heart Failure Research, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, NorwayAim. Inflammation is important in heart failure (HF). The role of the immune receptor toll-like receptor 9 (TLR9) in HF is not understood and not investigated in diastolic HF. We investigated the role of TLR9 in a murine diastolic HF model caused by cardiomyocyte SERCA2a excision. Methods and Results. We crossed SERCA2a KO and TLR9 KO mice to generate four mouse lines. Tamoxifen-induced cardiomyocyte SERCA2a gene excision was carried out in mice, causing diastolic HF. After 7.6 weeks, cardiac functions and dimensions were analyzed by echocardiography and heart tissues were processed. HF mice depleted of TLR9 demonstrated reduced survival compared to SERC2a KO mice, with a median life expectancy of 58 days compared to 63 days. Both HF groups displayed increased left atrium size, lung weight, fetal gene expressions, monocyte/macrophage infiltration, and fibrosis. However, there were no significant differences between the groups. Conclusion. In mice with SERCA2a KO-induced diastolic HF, the absence of TLR9 reduced median life expectancy. The cause remains elusive, as all investigated HF parameters were unaltered. Still, these findings support a salutary role of TLR9 in some subsets of HF conditions and underline the importance for future studies on the mechanisms of TLR9 in diastolic HF.http://dx.doi.org/10.1155/2017/9450439 |
| spellingShingle | Yangchen Dhondup Ivar Sjaastad Øystein Sandanger Jan Magnus Aronsen Muhammad Shakil Ahmed Håvard Attramadal Alexandra Vanessa Finsen Lili Zhang Trine Ranheim Katrine Alfsnes Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice Mediators of Inflammation |
| title | Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice |
| title_full | Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice |
| title_fullStr | Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice |
| title_full_unstemmed | Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice |
| title_short | Toll-Like Receptor 9 Promotes Survival in SERCA2a KO Heart Failure Mice |
| title_sort | toll like receptor 9 promotes survival in serca2a ko heart failure mice |
| url | http://dx.doi.org/10.1155/2017/9450439 |
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