Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression

Toshiomi Katsuki; Dai Kusumoto; Yohei Akiba; Mai Kimura; Jin Komuro; Takahiro Nakamura; Hisayuki Hashimoto; Thukaa Kouka; Kazuhisa Sugai; Yoshinori Katsumata; Masaki Miyasaka; Yutaka Suzuki; Junko Kuramoto; Yoshiaki Kubota; Keiichi Fukuda; Shinsuke Yuasa; Masaki Ieda

doi:10.1016/j.jacbts.2025.05.003

Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression

Toshiomi Katsuki
, Dai Kusumoto
, Yohei Akiba
, Mai Kimura
, Jin Komuro
, Takahiro Nakamura
, Hisayuki Hashimoto
, Thukaa Kouka
, Kazuhisa Sugai
, Yoshinori Katsumata
, Masaki Miyasaka
, Yutaka Suzuki
, Junko Kuramoto
, Yoshiaki Kubota
, Keiichi Fukuda
, Shinsuke Yuasa
, Masaki Ieda

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.

Original language	English
Article number	101308
Journal	JACC: Basic to Translational Science
Volume	10
Issue number	10
DOIs	https://doi.org/10.1016/j.jacbts.2025.05.003
Publication status	Published - 2025 Oct

Keywords

SCARB1
endothelial cells
fibroblasts
heart failure

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2025.05.003

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Katsuki, T., Kusumoto, D., Akiba, Y., Kimura, M., Komuro, J., Nakamura, T., Hashimoto, H., Kouka, T., Sugai, K., Katsumata, Y., Miyasaka, M., Suzuki, Y., Kuramoto, J., Kubota, Y., Fukuda, K., Yuasa, S., & Ieda, M. (2025). Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression. JACC: Basic to Translational Science, 10(10), Article 101308. https://doi.org/10.1016/j.jacbts.2025.05.003

Katsuki, T, Kusumoto, D, Akiba, Y, Kimura, M, Komuro, J, Nakamura, T, Hashimoto, H, Kouka, T, Sugai, K, Katsumata, Y, Miyasaka, M, Suzuki, Y, Kuramoto, J , Kubota, Y, Fukuda, K, Yuasa, S & Ieda, M 2025, 'Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression', JACC: Basic to Translational Science, vol. 10, no. 10, 101308. https://doi.org/10.1016/j.jacbts.2025.05.003

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title = "Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression",

abstract = "Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.",

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AU - Katsuki, Toshiomi

AU - Kusumoto, Dai

AU - Akiba, Yohei

AU - Kimura, Mai

AU - Komuro, Jin

AU - Nakamura, Takahiro

AU - Hashimoto, Hisayuki

AU - Kouka, Thukaa

AU - Sugai, Kazuhisa

AU - Katsumata, Yoshinori

AU - Miyasaka, Masaki

AU - Suzuki, Yutaka

AU - Kuramoto, Junko

AU - Kubota, Yoshiaki

AU - Fukuda, Keiichi

AU - Yuasa, Shinsuke

AU - Ieda, Masaki

PY - 2025/10

Y1 - 2025/10

N2 - Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.

AB - Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression. EC-specific Scarb1 knockout and systemic SCARB1 inhibition attenuated heart failure progression. In vitro and spatial omics analyses confirmed the role of SCARB1 in ECs and cell-cell interaction during heart failure progression. These findings highlight SCARB1 as a promising therapeutic target for EC-focused interventions.

KW - SCARB1

KW - endothelial cells

KW - fibroblasts

KW - heart failure

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Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression

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