Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling
Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constric...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/10/2636 |
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| author | Stephanie I. Bettink Jan-Christian Reil Andrey Kazakov Christina Körbel Dominic Millenaar Ulrich Laufs Bruno Scheller Michael Böhm Stephan H. Schirmer |
| author_facet | Stephanie I. Bettink Jan-Christian Reil Andrey Kazakov Christina Körbel Dominic Millenaar Ulrich Laufs Bruno Scheller Michael Böhm Stephan H. Schirmer |
| author_sort | Stephanie I. Bettink |
| collection | DOAJ |
| description | Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF<sup>−/−</sup>mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-β-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways. |
| first_indexed | 2024-03-09T20:37:34Z |
| format | Article |
| id | doaj.art-0ddb0f1f05944bdca36da8437194a209 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:37:34Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0ddb0f1f05944bdca36da8437194a2092023-11-23T23:06:17ZengMDPI AGBiomedicines2227-90592022-10-011010263610.3390/biomedicines10102636Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial RemodelingStephanie I. Bettink0Jan-Christian Reil1Andrey Kazakov2Christina Körbel3Dominic Millenaar4Ulrich Laufs5Bruno Scheller6Michael Böhm7Stephan H. Schirmer8Internal Medicine III, Saarland University, 66421 Homburg, GermanyMedical Clinic II, University Hospital Schleswig-Holstein, 23538 Lübeck, GermanyInternal Medicine III, Saarland University, 66421 Homburg, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInternal Medicine III, Saarland University, 66421 Homburg, GermanyDepartment of Cardiology, Leipzig University, 04103 Leipzig, GermanyInternal Medicine III, Saarland University, 66421 Homburg, GermanyInternal Medicine III, Saarland University, 66421 Homburg, GermanyInternal Medicine III, Saarland University, 66421 Homburg, GermanyPressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF<sup>−/−</sup>mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-β-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways.https://www.mdpi.com/2227-9059/10/10/2636TRIFfibrosishypertrophyinflammationafterload |
| spellingShingle | Stephanie I. Bettink Jan-Christian Reil Andrey Kazakov Christina Körbel Dominic Millenaar Ulrich Laufs Bruno Scheller Michael Böhm Stephan H. Schirmer Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling Biomedicines TRIF fibrosis hypertrophy inflammation afterload |
| title | Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling |
| title_full | Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling |
| title_fullStr | Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling |
| title_full_unstemmed | Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling |
| title_short | Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling |
| title_sort | inhibition of trif dependent inflammation decelerates afterload induced myocardial remodeling |
| topic | TRIF fibrosis hypertrophy inflammation afterload |
| url | https://www.mdpi.com/2227-9059/10/10/2636 |
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