Minju Seo, Ye-Ah Kim, Rokhyun Kim, Hyun Gu Lee, Man S Kim
miR-204-5p attenuates early inflammatory injury in CRAD by directly targeting IL-11 and suppressing IL-11-associated ERK1/2-NF-κB inflammatory signaling. The miR-204-5p/IL-11 axis may represent a potential regulatory pathway and therapeutic target for early inflammatory injury in CRAD.
Cardiac fibrosis, a hallmark of adverse remodeling following myocardial infarction (MI), markedly contributes to progressive heart failure. Severe tissue hypoxia within the ischemic heart activates hypoxia-inducible factor (HIF) signaling, thereby reshaping intercellular communication among non-myocytes. This mini-review presents the latest evidence on hypoxia-driven fibrosis through three processes: (i) fibroblast activation and myofibroblast differentiation, (ii) macrophage polarization and paracrine effects, and (iii) endothelial-to-mesenchymal transition (EndMT). Recent single-cell transcriptomics studies have revealed fibroblast/immune cell heterogeneity post-injury, while metabolic shifts (e.g., glycolytic reprogramming, lactate-histone lactylation, and glutamine persistence) link hypoxia to the epigenetic regulation of fibrosis. Novel therapies, including lactate-scavenging biomaterials, eNAMPT neutralization, and timed metalloproteinase inhibition, show promise in targeting these pathways. A deeper understanding of hypoxia-mediated crosstalk may lead to the development of strategies to mitigate maladaptive fibrosis while preserving reparative scarring following MI.