AI Insight
This study identifies a previously unknown pathway linking tricuspid valve regurgitation to heart failure progression through immune system activation. Researchers found that tricuspid regurgitation causes venous congestion that damages the intestinal barrier, leading to increased circulating monocytes that produce Interleukin-6 (IL-6), which drives inflammation and scarring in the heart. Blocking IL-6 improved cardiac function in animal models, and repairing the tricuspid valve in patients reduced IL-6 levels, suggesting this immune pathway could be therapeutically targeted.
Why it matters
These findings could explain why some heart failure patients deteriorate despite standard treatments and identify tricuspid regurgitation patients as a specific group who might benefit from IL-6-blocking therapies. The discovery of this gut-heart immune connection opens new therapeutic avenues for a condition that affects millions of heart failure patients worldwide.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
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.