Key result
Selenop deletion attenuates pressure overload-induced cardiac hypertrophy, dysfunction, and fibrosis in preclinical heart failure models.
Why the study?
The role of the liver-heart axis in cardiac remodeling is poorly understood, and the causal, tissue-specific contributions of the hepatokine selenoprotein P to HF-related cardiac remodeling remained unclear.
Does global or hepatocyte-specific Selenoprotein P deletion attenuate pressure overload-induced cardiac remodeling in mice undergoing transverse aortic constriction?
Does global or hepatocyte-specific Selenoprotein P deletion attenuate pressure overload-induced cardiac remodeling in mice undergoing transverse aortic constriction?
Hepatocyte-derived selenoprotein P drives adverse cardiac remodeling and TGF-β-related profibrotic signaling under pressure overload in mice, highlighting a novel liver-heart axis mechanism in heart failure progression.
Answers are grounded in this paper and cite their sources.
Extends preclinical liver-heart signaling evidence in remodeling; leaves open relevance to human HF before any clinical consideration.
Background Heart failure (HF) is increasingly recognized as a systemic disorder involving inter-organ communication. However, the role of the liver-heart axis in cardiac remodeling remains poorly understood. Selenoprotein P (Selenop), a hepatokine involved in systemic metabolic regulation, has been associated with HF, but its causal and tissue-specific contributions to cardiac remodeling remain unclear. Methods and results We investigated the role of Selenop in pressure overload–induced cardiac remodeling using a transverse aortic constriction (TAC) in global and hepatocyte-specific Selenop knockout mice. TAC increased hepatic Selenop expression and circulating Selenop protein without altering cardiac Selenop expression. These changes were accompanied by reduced hepatic Akt and FoxO1 phosphorylation. Global Selenop deficiency improved survival and attenuated TAC-induced cardiac hypertrophy, pulmonary congestion, systolic dysfunction, and interstitial fibrosis. Transcriptomic and quantitative RT-PCR analyses showed that Selenop deficiency reduced cardiac Tgfb1 expression and attenuated TGF-β-associated profibrotic genes, including extracellular matrix-related genes. Hepatocyte-specific Selenop deletion markedly reduced circulating Selenop and attenuated TAC-induced cardiac hypertrophy, pulmonary congestion, systolic dysfunction, and profibrotic gene expression. Conclusions Hepatocyte-derived Selenop contributes to adverse cardiac remodeling under pressure overload and is associated with a TGF-β-related profibrotic transcriptional response in the heart. These findings support Selenop-mediated liver-heart communication as a potential mechanism of HF progression.
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Usui et al. (2026) studied Pressure overload-induced cardiac remodeling / Heart failure. Global and hepatocyte-specific Selenoprotein P (Selenop) deficiency / deletion vs. Control mice undergoing transverse aortic constriction (TAC) was evaluated on Survival, TAC-induced cardiac hypertrophy, pulmonary congestion, systolic dysfunction, and interstitial fibrosis. Global and hepatocyte-specific Selenop deletion attenuated TAC-induced cardiac hypertrophy, pulmonary congestion, systolic dysfunction, and TGF-β-related profibrotic gene expression in mice.
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