{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:55:20Z","timestamp":1781758520456,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atherosclerosis is a vascular disease characterized by lipid deposition, chronic inflammation, and cell death. Necroptosis, a form of programmed necrosis, plays a critical role in atherosclerosis progression. This study investigates the expression of the deubiquitinating enzyme OTUD7B in atherosclerosis and its mechanism in regulating vascular injury via the RIPK1-mediated necroptosis pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An atherosclerosis model was established in mice fed a high-fat diet combined with partial carotid ligation. OTUD7B and necroptosis-related proteins RIPK1, RIPK3, and phosphorylated MLKL (p-MLKL) were detected in arterial tissues.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , a necroptosis model was induced in human aortic smooth muscle cells (HA-SMCs) using the TSZ protocol. OTUD7B was knocked down to assess cell viability, inflammatory cytokine levels, and necroptosis. OTUD7B knockdown and RIPK1 co-overexpression were employed to validate its protective effects and dependency\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OTUD7B was significantly upregulated in plaques of atherosclerosis mice, concomitant with increased expression and phosphorylation of RIPK1 and RIPK3, as well as elevated p-MLKL levels. TUNEL staining and ELISA confirmed elevated necroptosis and inflammation.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , OTUD7B knockdown markedly alleviated HA-SMC injury, suppressed the expression and phosphorylation of necroptosis markers, and reduced IL-1\u03b2\/TNF-\u03b1 release.\n                      <jats:italic>In vivo<\/jats:italic>\n                      OTUD7B knockdown attenuated plaque formation, lipid deposition, necroptosis, and inflammation. Mechanistically, RIPK1 overexpression significantly reversed the protective effects of OTUD7B knockdown, restoring RIPK1\/RIPK3 phosphorylation and downstream signaling, indicating its functional dependency on the RIPK1 pathway. Co-immunoprecipitation further confirmed a direct OTUD7B-RIPK1 interaction, facilitating downstream signaling activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OTUD7B exacerbates necroptosis and inflammation in vascular smooth muscle cells by activating the RIPK1-RIPK3-MLKL axis, thereby playing a detrimental role in AS. This study identifies OTUD7B as a potential therapeutic target for atherosclerosis intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1749659","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:35:09Z","timestamp":1781757309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["OTUD7B exacerbates atherosclerosis by promoting RIPK1-dependent vascular smooth muscle cell necroptosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Linfei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Haiyan People\u2019s Hospital","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Haiyan People\u2019s Hospital","place":["Jiaxing, 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