{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:27:56Z","timestamp":1786350476976,"version":"build-2736575974"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fcell.2026.1814166","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T07:31:37Z","timestamp":1786347097000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypoxia-driven crosstalk among cardiac fibroblasts, macrophages, and endothelial cells in cardiac fibrosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Minju","family":"Seo","sequence":"first","affiliation":[{"name":"Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Department of Medicine, Kyung Hee University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Department of Biomedical Science and Technology, Graduate School, Kyung Hee University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokhyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Space Biomedical Science, NEXUS Institute, Kyung Hee University","place":["Yongin-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Department of Medicine, Kyung Hee University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Biomedical Science and Technology, Graduate School, Kyung Hee University","place":["Seoul, Republic of Korea"]},{"name":"Center for Space Biomedical Science, NEXUS Institute, Kyung Hee University","place":["Yongin-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.1038\/s41467-019-10859-w","article-title":"Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M","volume":"10","author":"Abe","year":"2019","journal-title":"Nat. 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