Browsing by Author "Ito, Jumpei"

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    NF-κB activation in cardiac fibroblasts results in the recruitment of inflammatory Ly6Chi monocytes in pressure-overloaded hearts
    (American Association for the Advancement of Science, 2021) Abe, Hajime; Tanada, Yohei; Omiya, Shigemiki; Podaru, Mihai-Nicolae; Murakawa, Tomokazu; Ito, Jumpei; Shah, Ajay M.; Conway, Simon J.; Ono, Masahiro; Otsu, Kinya; Pediatrics, School of Medicine
    Heart 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.