Key result
TRIF deficiency in mice subjected to trans-aortic constriction reduced myocardial accumulation of inflammatory cells, slowed left-ventricular wall thickening, and decreased interstitial fibrosis.
Why the study?
Pressure-overload-induced cardiac hypertrophy can lead to heart failure, but the role of TRIF during afterload-induced myocardial remodeling remained to be characterized.
TRIF is a key adapter protein in early maladaptive cardiac remodeling, and its deficiency decelerates afterload-induced myocardial hypertrophy and fibrosis in a murine model.
TRIF may modulate early cytokine response in pressure-overload remodeling; leaves open therapeutic targeting in HF.
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−/−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.
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Bettink et al. (2022) studied Pressure-overload-induced cardiac hypertrophy. TRIF deficiency vs. Wild-type controls was evaluated on Myocardial remodeling and inflammation. TRIF deficiency in mice subjected to trans-aortic constriction reduced myocardial accumulation of inflammatory cells, slowed left-ventricular wall thickening, and decreased interstitial fibrosis.
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