Hepatocyte-derived selenoprotein P contributes to pressure overload–induced cardiac remodeling
- 1Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
- 2Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
- 3Information-Based Medicine Development, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
Abstract
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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BibTeX
@article{usui2026hepatocytederived,
title = {{Hepatocyte-derived selenoprotein P contributes to pressure overload–induced cardiac remodeling}},
author = {Soichiro Usui and Shinichiro Takashima and Oto Inoue and Chiaki Goten and Yusuke Takeda and Daiki Hashimuko and Kosei Yamaguchi and Yusuke Shinjo and Ayano Nomura and Toshinari Takamura and Shuichi Kaneko and Masayuki Takamura},
journal = {Biochemistry and Biophysics Reports},
year = {2026},
month = oct,
doi = {10.1016/j.bbrep.2026.102854},
url = {https://doi.org/10.1016/j.bbrep.2026.102854},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hepatocyte-derived selenoprotein P contributes to pressure overload–induced cardiac remodeling
AU - Soichiro Usui
AU - Shinichiro Takashima
AU - Oto Inoue
AU - Chiaki Goten
AU - Yusuke Takeda
AU - Daiki Hashimuko
AU - Kosei Yamaguchi
AU - Yusuke Shinjo
AU - Ayano Nomura
AU - Toshinari Takamura
AU - Shuichi Kaneko
AU - Masayuki Takamura
PY - 2026
DA - 2026/10/26
JO - Biochemistry and Biophysics Reports
DO - 10.1016/j.bbrep.2026.102854
UR - https://doi.org/10.1016/j.bbrep.2026.102854
AB - 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.
SN - 2405-5808
ER -