{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:59:34Z","timestamp":1791464374374,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701167"],"award-info":[{"award-number":["81701167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030310360"],"award-info":[{"award-number":["2017A030310360"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Atherosclerosis (AS) is closely linked to endothelial cell (EC) senescence and mitochondrial dysfunction, which impair vascular repair. Resveratrol (RSV) has antioxidant, anti\u2010inflammatory, and pro\u2010angiogenic effects, but its clinical use is restricted by poor bioavailability. This study aimed to construct a platelet membrane\u2010coated resveratrol nanosystem (PM@RSV NPs) and investigate its mechanism of action in delaying the progression of AS by activating FOXM1 to improve mitochondrial function, inhibit EC senescence, and promote vascular regeneration. PM@RSV NPs were prepared using a solvent evaporation method combined with membrane\u2010coating technology, and gene expression profiles and key regulatory networks were analyzed through RNA sequencing (RNA\u2010seq), gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator (LASSO) regression. In\u00a0vitro, PM@RSV NPs enhanced mitochondrial membrane potential and ATP generation while decreasing ROS accumulation and the number of SA\u2010\u03b2\u2010Gal\u2010positive cells, accompanied by FOXM1 upregulation in ECs. In\u00a0vivo experiments demonstrated that PM@RSV NPs significantly reduced plaque area, improved mitochondrial function, decreased levels of senescence markers, and promoted vascular regeneration via FOXM1 regulation. In addition, PM@RSV NPs preferentially accumulated in ox\u2010LDL\u2010injured MAECs and AS lesion\u2010associated vascular endothelium, mainly through platelet\u2010membrane adhesion proteins such as GPV and P\u2010selectin; their biosafety was evaluated by EC viability\/apoptosis assays, histological examination of major organs, and serum biochemical indices of liver and kidney function. This study confirmed that PM@RSV NPs improved mitochondrial function, inhibited endothelial senescence, and enhanced vascular regeneration by activating FOXM1, offering a novel therapeutic strategy for treating AS.<\/jats:p>","DOI":"10.1111\/acel.70632","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:24:35Z","timestamp":1784661875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Study of Platelet Membrane\u2010Coated Resveratrol Nanosystem in Mitochondrial Dysfunction and Endothelial Senescence During Atherosclerotic Lesion Development via\n                    <scp>FOXM1<\/scp>\n                    Activation"],"prefix":"10.1111","volume":"25","author":[{"given":"Li","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexin","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-7183","authenticated-orcid":false,"given":"Bing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2019.03.017"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-07-0413"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015160"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-024-00773-4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2023.116656"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00275"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26144367"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318353"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14010070"},{"issue":"1","key":"e_1_2_12_14_1","article-title":"Abstract 1131: Delivery of Allogeneic Mitochondria Reverses Signatures of Endothelial Aging & Senescence","volume":"44","author":"Headley C. A.","year":"2024","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1970.10488634"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2021.11.005"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2022.07.012"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2023.03.007"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126808"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2011.09.004"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2019.01.022"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202308239"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2024.0201-1"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102146"},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/s41587-024-02327-8","article-title":"Counteracting Tissue Aging Through TERT Activation","volume":"42","author":"Marchal I.","year":"2024","journal-title":"Nature Biotechnology"},{"key":"e_1_2_12_26_1","first-page":"894","article-title":"The Role of Platelets in Atherosclerosis: A Historical Review","volume":"51","author":"Momi S.","year":"2024","journal-title":"Seminars in Thrombosis and Hemostasis"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1422686"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105725"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315160"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2024.111931"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900078-MCP200"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003300588-2"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26031379"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae933"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03412-z"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.29296\/24999490-2022-04-02"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00815-5"},{"key":"e_1_2_12_38_1","first-page":"30","article-title":"Inflammatory Cytokines in the Pathogenesis of Atherosclerosis","volume":"69","author":"Takahashi M.","year":"2011","journal-title":"Nihon Rinsho"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101440"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015379"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57538-7"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd10090382"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01561-6"},{"key":"e_1_2_12_45_1","first-page":"1","volume-title":"Handbook of Experimental Pharmacology","author":"Yin Y.","year":"2024"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102828"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1408651"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00892.2013"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.910580"},{"key":"e_1_2_12_50_1","first-page":"2575","article-title":"Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging","volume":"16","author":"Zhang H.","year":"2024","journal-title":"Aging and Disease"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57467-5"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-012-0228-0"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-024-01281-0"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4TB02091J"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70632","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70632","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:10:45Z","timestamp":1787321445000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/acel.70632"],"URL":"https:\/\/doi.org\/10.1111\/acel.70632","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"2026-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70632"}}