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Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism 期刊论文

编号：

632CF0477B52A3F2E98375F4A37E05C9
作者：

Wu, Yufei^[1,2];Yang, Xiaomei(杨晓玫)^[3,4]Bai, Yu^[5,6];Li, Chenze^[7];Wang, Peng^[8];Xu, Qing^[9];Li, Hui^[10,11];Rao, Xiaoli^[12];Xu, Yangkai^[1,2];Chen, Jie^[1,2];Cao, Huanhuan^[1,2];Zhang, Qi^[1,2];Zhao, Mingming^[10,11];Zhan, Rui^[13];Fan, Xue^[14];Hou, Yuedong(侯跃东)^[3]Liu, Jie^[15,16];Lu, Hong S^[17,18];Wang, Tianyun^[12];Gao, Wei Dong(高卫东)^[19]Huang, Linzhang^[20];Xiao, Han^[10,11];Zu, Lingyun^[10,11,21];Daugherty, Alan^[17,18];Xu, Mingguo^[2,22];Zheng, Lemin^[1,2,23];
语种：

英文
期刊：

EMBO MOLECULAR MEDICINE ISSN：1757-4676 2026 年 ; 2026 APR 13
收录：
关键词：

Heart Failure with Preserved Ejection Fraction Cardiac Microvascular Endothelial Dysfunction Scavenger Receptor Class B Type I (SR-B1) Chemokine C-X-C Motif Chemokine Ligand 10 (CXCL10)
摘要：

Cardiac microvascular endothelial cells (CMECs) dysfunction is a well-recognized mediator of heart failure with preserved ejection fraction (HFpEF), but the underlying mechanism remains unclear. Here we find that scavenger receptor class B type I (SR-B1) is predominantly expressed in CMECs and decreased significantly in HFpEF. Endothelial-specific SR-B1 deficiency exacerbates cardiac pathological remodeling and diastolic dysfunction in HFpEF, which can be prevented by endothelial SR-B1 reconstitution through adeno-associated virus serotype 1 (AAV1)-mediated delivery in endothelial-specific SR-B1-deficient mice. Single-cardiac-endothelial-cell transcriptomics and lineage-tracing system reveal that inflammatory CMECs subcluster activation is responsible for the deteriorating HFpEF progression induced by endothelial SR-B1 loss, rather than endothelial-to-mesenchymal transition. Mechanistically, SR-B1 loss drives increased CXCL10 secretion, which orchestrates CMECs activation and CXCR3-positive T-cell cardiotropism to promote diastolic dysfunction-a process associated with endothelial IRF1 activation. Most importantly, the SR-B1-CXCL10-CXCR3 axis is activated in human HFpEF cardiac tissue, and the elevated CXCL10 level in plasma is independently associated with a higher HFpEF prevalence. This study uncovers that activation of the SR-B1-CXCL10-CXCR3 axis in CMECs aggravates HFpEF pathogenesis through the accumulation of CXCR3-positive T-cells in hearts.
推荐引用方式
GB/T 7714：

Wu Yufei,Yang Xiaomei,Bai Yu, et al. Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism [J].EMBO MOLECULAR MEDICINE,2026.
APA：

Wu Yufei,Yang Xiaomei,Bai Yu,Li Chenze,&Zheng Lemin.(2026).Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism .EMBO MOLECULAR MEDICINE.
MLA：

Wu Yufei, et al. "Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism" .EMBO MOLECULAR MEDICINE(2026).
入库时间：

4/29/2026 11:02:57 PM
更新时间：

4/30/2026 1:49:54 AM

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