biostudies-literatureUnknown10(10)Katsuki TTakeda Science FoundationJapan Agency for Medical Research and DevelopmentBayerMSDInappropriate 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.JACC. Basic to translational science101308https://www.ebi.ac.uk/biostudies/studies/S-EPMC12665495biostudies-literatureInhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression.PMC12665495Kuramoto JFukuda KKomuro JKatsuki TKubota YIeda MMiyasaka MKimura MKusumoto DAkiba YSuzuki YYuasa SNakamura TKouka TSugai KKatsumata YHashimoto HfalseInhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-Induced Heart Failure Progression.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.2025-01-01T00:00:00Z2025 Oct2026-06-06T15:02:17.269Z2026-06-01T03:10:37.553ZS-EPMC126654954077290010.1016/j.jacbts.2025.05.003