Abe, HajimeTanada, YoheiOmiya, ShigemikiPodaru, Mihai-NicolaeMurakawa, TomokazuIto, JumpeiShah, Ajay M.Conway, Simon J.Ono, MasahiroOtsu, Kinya2024-12-092024-12-092021Abe H, Tanada Y, Omiya S, et al. NF-κB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6Chi monocytes in pressure-overloaded hearts. Sci Signal. 2021;14(704):eabe4932. doi:10.1126/scisignal.abe4932https://hdl.handle.net/1805/44849Heart failure is a major public health problem, and inflammation is involved in its pathogenesis. Inflammatory Ly6Chi monocytes accumulate in mouse hearts after pressure overload and are detrimental to the heart; however, the types of cells that drive inflammatory cell recruitment remain uncertain. Here, we showed that a distinct subset of mouse cardiac fibroblasts became activated by pressure overload and recruited Ly6Chi monocytes to the heart. Single-cell sequencing analysis revealed that a subset of cardiac fibroblasts highly expressed genes transcriptionally activated by the transcription factor NF-κB, as well as C-C motif chemokine ligand 2 (Ccl2) mRNA, which encodes a major factor in Ly6Chi monocyte recruitment. The deletion of the NF-κB activator IKKβ in activated cardiac fibroblasts attenuated Ly6Chi monocyte recruitment and preserved cardiac function in mice subjected to pressure overload. Pseudotime analysis indicated two single-branch trajectories from quiescent fibroblasts into inflammatory fibroblasts and myofibroblasts. Our results provide insight into the mechanisms underlying cardiac inflammation and fibroblast-mediated inflammatory responses that could be therapeutically targeted to treat heart failure.en-USPublisher PolicyFibroblastsGene expression regulationMonocytesArticle