{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:19Z","timestamp":1787807899100,"version":"build-2784847793"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02216513"],"award-info":[{"award-number":["RS-2025-02216513"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2025-02216513"],"award-info":[{"award-number":["RS-2025-02216513"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0227as991","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Foam cells are central to atherosclerotic plaque development, but their pathological significance in advanced lesions extends beyond lipid accumulation. Under chronic exposure to oxidized lipoproteins, cholesterol crystals, inflammatory cytokines, hypoxia, lysosomal stress, and mitochondrial injury, lipid-loaded foam cells of macrophage and vascular smooth muscle cell (VSMC) origin may acquire maladaptive stress phenotypes. In this focused review, we propose a redox-threshold model, defined as the transition point at which mitochondrial antioxidant and metabolic buffering capacity is exceeded, allowing lipid peroxide accumulation to shift senescence-like foam cells toward ferroptosis susceptibility and defective plaque resolution. Progressive mitochondrial reactive oxygen species (ROS) accumulation, impaired NADPH-dependent antioxidant buffering, defective glutathione and thioredoxin recycling, mitophagy impairment, and reduced GPX4-mediated lipid peroxide detoxification may converge to promote iron-dependent lipid peroxidation. If lipid-peroxidized or dying foam cells are not efficiently cleared, oxidized lipids, cellular debris, and inflammatory signals accumulate, promoting secondary necrosis, necrotic core expansion, plaque non-resolution, and instability. We explicitly distinguish established processes from mechanistically supported inferences and hypothesis-generating links, emphasizing that the complete senescence-like stress-to-ferroptosis-to-non-resolution sequence remains a testable framework rather than an established linear pathway. This focused framework suggests that advanced plaque stabilization may require strategies that preserve mitochondrial redox resilience, limit ferroptotic lipid peroxidation, and enhance efferocytosis-mediated resolution.<\/jats:p>","DOI":"10.3390\/antiox15091061","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:19Z","timestamp":1787657239000},"page":"1061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Redox Failure Links Senescence-like Foam Cell Stress to Ferroptosis and Plaque Non-Resolution in Atherosclerosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Phyu Phyu","family":"Khin","sequence":"first","affiliation":[{"name":"Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0691-2374","authenticated-orcid":false,"given":"Hla Myat Mo","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-6089","authenticated-orcid":false,"given":"Cuk-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. 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