Biology subjects

Quadt, L.

Publications and source records attributed to Quadt, L..

2 recordsLinked to original sources

bioRxiv2026

Tricuspid valve regurgitation accelerates heart failure via a cardio-intestinal innate immune circuit

Activation of the immune system impacts the progression of heart failure (HF), but the underlying mechanisms remain incompletely understood. Here, we identify a cardio-intestinal innate immune axis that links systemic venous congestion to myocardial inflammation, fibrosis, and functional decline. Using single-cell and single-nucleus transcriptomic profiling in patients and mice with tricuspid regurgitation (TR), we demonstrate that TR disrupts intestinal barrier integrity and elicits expansion of circulating monocytes which in turn orchestrate pathological crosstalk between the right and left heart. Monocyte-derived Interleukin-6 (IL-6) emerged as a key mediator of TR-driven myocardial fibrosis and dysfunction. Blockade of IL-6 attenuated cardiac fibrosis and improved cardiac function. In patients, catheter-based repair of TR resulted in reduced IL-6 levels. Together, these findings establish cardio-intestinal innate immunity as a mechanism linking altered hemodynamics to left ventricular remodeling and nominate TR patients as a selective target population for IL-6-directed therapy in HF. One Sentence SummaryThis work mechanistically resolves the heart-gut axis in tricuspid valve regurgitation, and its impact on heart failure progression as mediated by Interleukin-6.

immunology↗

bioRxiv2024

A hierarchical Bayesian model reveals increased precision weighting for afferent cardiac signals, and reduced anxiety, as a function of interoceptive training

Perceptual accuracy for interoceptive signals, such as heartbeats, varies in a trait-like manner across individuals and may influence the capacity for emotion regulation and vulnerability to affective symptoms, notably anxiety. Here, we demonstrate that an interoceptive training protocol improved perceptual accuracy in two tasks of heartbeat perception and reduced both state and trait anxiety in a subclinical sample, extending previous findings in autistic adults. Computational modelling indicated that accuracy improvement in the heartbeat discrimination task was associated with increases in the internal reliability estimate for interoceptive signals - their precision weighting - while a lower-level parameter representing noise in the interoceptive signal itself (which influences speed of learning) moderated this precision weighting improvement. Reductions in both state and trait anxiety in the training group were uniquely explained by computational parameter estimates, and not by conventional accuracy measures. These findings indicate that trait-like differences in interoceptive processing are modifiable and can be targeted to alleviate anxiety symptoms, and that interoceptive interventions may be best guided by a computational phenotyping approach.

neuroscience↗