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- (TRIF) during afterload-induced myocardial remodeling. After transaortic
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 TRIFmice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent
cytokines. Through the modulation of the TGF-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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:92954 |
| Date | 06 August 2024 |
| Creators | Bettink, Stephanie I., Reil, Jan-Christian, Kazakov, Andrey, Körbel, Christina, Millenaar, Dominic, Laufs, Ulrich, Scheller, Bruno, Böhm, Michael, Schirmer, Stephan H. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2227-9059, 10.3390/biomedicines10102636 |
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