{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T10:06:48Z","timestamp":1779012408795,"version":"3.51.4"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atherosclerotic cardiovascular disease is still a major cause for the increasing mortality worldwide. The elevated metabolite N\u2010acetylneuraminic acid (Neu5Ac) was considered one of the important risk factors responsible for the initiation of endothelial impairment, then participated in atherosclerosis progression. However, the reason for inducing Neu5Ac accumulation as well as its underlying mechanism remains unclear. Here, we applied human umbilical vein endothelial cells (HUVECs) and ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice to investigate the key genes responsible for Neu5Ac accumulation as well as its regulation mechanism. We found that tumour necrosis factor alpha (TNF\u2010\u03b1) could induce Neu5Ac metabolism disorder and increase Neu5Ac level, accompanied by the increasing levels of inflammatory markers in HUVECs. Further, we found that sialidase NEU3 was significantly up\u2010regulated, accompanied by Neu5Ac accumulation. NEU3\n                    <jats:sup>siRNA<\/jats:sup>\n                    in HUVECs could significantly reduce Neu5Ac levels and alleviate endothelial inflammation. In contrast, the addition of exogenous Neu5Ac reversed such phenomenon. Furthermore, we noted that NEU3 was highly expressed in atherosclerotic plaques from ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice as well as atherosclerotic patient tissues. Mechanically, we found that the transcription factor specificity protein 3 (SP3) was activated in HUVECs, responsible for Neu5Ac metabolism disorder. While RNA interference of SP3 could decrease NEU3 mRNA level and reduce endothelial inflammatory injury, indicating that SP3 might be the upstream regulatory factor of NEU3. Together, these findings identified the key role of NEU3 in regulating Neu5Ac metabolism associated with endothelial function, as well as its potential regulation mechanism. Targeting SP3\/NEU3 seems to be a potential therapeutic strategy for such diseases with Neu5Ac accumulation like atherosclerosis (AS).\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71169","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:27:26Z","timestamp":1778578046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sialidase Neu3 Induced Sialic Acid Disorder and Promoted Vascular Endothelial Injury Through Transcription Factor\n                    <scp>SP3<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4232-793X","authenticated-orcid":false,"given":"Yining","family":"Lu","sequence":"first","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xiang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongchuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research  Chongqing 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