• Media type: E-Article
  • Title: Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling
  • Contributor: Bettink, Stephanie I. [Author]; Reil, Jan-Christian [Author]; Kazakov, Andrey [Author]; Körbel, Christina [Author]; Millenaar, Dominic [Author]; Laufs, Ulrich [Author]; Scheller, Bruno [Author]; Böhm, Michael [Author]; Schirmer, Stephan H. [Author]
  • Published: Basel : MDPI, [2024]
  • Published in: Biomedicines ; 10,10 (2022), Seite 1-18
  • Language: English
  • DOI: 10.3390/biomedicines10102636
  • Keywords: afterload 1. Introduction ; inflammation ; hypertrophy ; TRIF ; fibrosis
  • Origination:
  • Footnote:
  • Description: Pressure-overload-induced cardiac hypertrophy represents one cause of the developmentof heart failure. The aim of this study is to characterize the influence of the TIR-domain-containingadapter-inducing interferon- (TRIF) during afterload-induced myocardial remodeling. After transaorticconstriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloiddifferentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokineexpression appeared within the first week and decreased to its control level within five weeks. Whilecardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cellswas lower in TRIFmice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependentcytokines. 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 witha decreased expression of proapoptotic proteins. In echocardiography and working heart analyses,TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces theejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatorycytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiacremodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatoryand fibrotic signal transduction pathways.
  • Access State: Open Access
  • Rights information: Attribution (CC BY)