TLR7 Inhibition Limits Ischemic Cardiac Injury by Disrupting ITGAM-Dependent Immune-Endothelial Interactions.

Authors

Yijia Li, Yang Yang, Chanhee Park, Boyang Ren, Ruoxing Li, Amol Shetty, Brittney Williams, Ziyi Li, Lin Zou, Wei Chao

Published in

JACC. Basic to translational science. Volume 11. Issue 8. Pages 101626. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Percutaneous coronary intervention, such as stenting, restores coronary perfusion after myocardial ischemia but also induces ischemia-reperfusion (I/R) injury, in part driven by innate immune activation. Here, we identified Toll-like receptor 7 (TLR7), an endosomal sensor of single-stranded RNA, as a key mediator of postischemic inflammation. Genetic deletion or pharmacologic inhibition of TLR7 with enpatoran reduced inflammation and myocardial infarction (MI) size and improved cardiac function 24 hours after I/R in mice. Single-nucleus RNA sequencing demonstrated coordinated induction of TLR7-responsive inflammatory endothelial and myeloid cell programs, including increased endothelial ITGAM expression and leukocyte adhesion. TLR7/8 activation promoted ITGAM-dependent endothelial-leukocyte interactions under shear stress, whereas ITGAM blockade reduced immune cell infiltration and limited MI injury. These findings identify the TLR7-ITGAM signaling axis as a central driver of endothelial-leukocyte crosstalk in myocardial I/R injury and support TLR7 inhibition as a promising therapeutic strategy to mitigate ischemic MI after percutaneous coronary intervention.

PMID:
42447539
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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