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NF-κB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6Chi monocytes in pressure-overloaded hearts

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)eabe4932
JournalScience Signaling
Issue number704
Early online date12 Oct 2021
Accepted/In press24 Sep 2021
E-pub ahead of print12 Oct 2021
Published12 Oct 2021


  • HAjime

    HAjime.pdf, 18.9 MB, application/pdf

    Uploaded date:01 Oct 2021

King's Authors


Heart failure is a major public health problem and inflammation is involved in its
pathogenesis. Inflammatory Ly6C 37 hi monocytes accumulate in mouse hearts after pressure overload and are detrimental to the heart; however, the types of cells that drive inflammatory cell recruitment remains uncertain. Here, we showed that a distinct subset of mouse cardiac
fibroblasts became activated by pressure overload and recruited Ly6C 40 hi 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 CC 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 Ly6C 45 hi 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

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