Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice.
<h4>Aim</h4>Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflamm...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139715&type=printable |
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| author | Yangchen Dhondup Ivar Sjaastad Helge Scott Øystein Sandanger Lili Zhang Solveig Bjærum Haugstad Jan Magnus Aronsen Trine Ranheim Sigve Dhondup Holmen Katrine Alfsnes Muhammad Shakil Ahmed Håvard Attramadal Lars Gullestad Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge |
| author_facet | Yangchen Dhondup Ivar Sjaastad Helge Scott Øystein Sandanger Lili Zhang Solveig Bjærum Haugstad Jan Magnus Aronsen Trine Ranheim Sigve Dhondup Holmen Katrine Alfsnes Muhammad Shakil Ahmed Håvard Attramadal Lars Gullestad Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge |
| author_sort | Yangchen Dhondup |
| collection | DOAJ |
| description | <h4>Aim</h4>Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflammation, caused by sustained Toll-like receptor 9 activation, on established diastolic heart failure.<h4>Methods and results</h4>Diastolic heart failure was established in 8-10 week old cardiomyocyte specific, inducible SERCA2a knock out (i.e., SERCA2a KO) C57Bl/6J mice. Four weeks after conditional KO, mice were randomized to receive Toll-like receptor 9 agonist (CpG B; 2μg/g body weight) or PBS every third day. After additional four weeks, echocardiography, phase contrast magnetic resonance imaging, histology, flow cytometry, and cardiac RNA analyses were performed. A subgroup was followed, registering morbidity and death. Non-heart failure control groups treated with CpG B or PBS served as controls. Our main findings were: (i) Toll-like receptor 9 activation (CpG B) reduced life expectancy in SERCA2a KO mice compared to PBS treated SERCA2a KO mice. (ii) Diastolic function was lower in SERCA2a KO mice with Toll-like receptor 9 activation. (iii) Toll-like receptor 9 stimulated SERCA2a KO mice also had increased cardiac and systemic inflammation.<h4>Conclusion</h4>Sustained activation of Toll-like receptor 9 causes cardiac and systemic inflammation, and deterioration of SERCA2a depletion-mediated diastolic heart failure. |
| format | Article |
| id | doaj-art-430cff5cb94d46239bb2049bbba4ceda |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-430cff5cb94d46239bb2049bbba4ceda2025-08-20T03:11:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013971510.1371/journal.pone.0139715Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice.Yangchen DhondupIvar SjaastadHelge ScottØystein SandangerLili ZhangSolveig Bjærum HaugstadJan Magnus AronsenTrine RanheimSigve Dhondup HolmenKatrine AlfsnesMuhammad Shakil AhmedHåvard AttramadalLars GullestadPål AukrustGeir ChristensenArne YndestadLeif Erik Vinge<h4>Aim</h4>Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflammation, caused by sustained Toll-like receptor 9 activation, on established diastolic heart failure.<h4>Methods and results</h4>Diastolic heart failure was established in 8-10 week old cardiomyocyte specific, inducible SERCA2a knock out (i.e., SERCA2a KO) C57Bl/6J mice. Four weeks after conditional KO, mice were randomized to receive Toll-like receptor 9 agonist (CpG B; 2μg/g body weight) or PBS every third day. After additional four weeks, echocardiography, phase contrast magnetic resonance imaging, histology, flow cytometry, and cardiac RNA analyses were performed. A subgroup was followed, registering morbidity and death. Non-heart failure control groups treated with CpG B or PBS served as controls. Our main findings were: (i) Toll-like receptor 9 activation (CpG B) reduced life expectancy in SERCA2a KO mice compared to PBS treated SERCA2a KO mice. (ii) Diastolic function was lower in SERCA2a KO mice with Toll-like receptor 9 activation. (iii) Toll-like receptor 9 stimulated SERCA2a KO mice also had increased cardiac and systemic inflammation.<h4>Conclusion</h4>Sustained activation of Toll-like receptor 9 causes cardiac and systemic inflammation, and deterioration of SERCA2a depletion-mediated diastolic heart failure.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139715&type=printable |
| spellingShingle | Yangchen Dhondup Ivar Sjaastad Helge Scott Øystein Sandanger Lili Zhang Solveig Bjærum Haugstad Jan Magnus Aronsen Trine Ranheim Sigve Dhondup Holmen Katrine Alfsnes Muhammad Shakil Ahmed Håvard Attramadal Lars Gullestad Pål Aukrust Geir Christensen Arne Yndestad Leif Erik Vinge Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. PLoS ONE |
| title | Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. |
| title_full | Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. |
| title_fullStr | Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. |
| title_full_unstemmed | Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. |
| title_short | Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice. |
| title_sort | sustained toll like receptor 9 activation promotes systemic and cardiac inflammation and aggravates diastolic heart failure in serca2a ko mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0139715&type=printable |
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