{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:17:49Z","timestamp":1792059469770,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":165,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370614"],"award-info":[{"award-number":["81370614"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low\u2010density lipoprotein\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2\u2010glycoprotein I\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2\u2010glycoprotein I antibody (oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP\u2010GFP\u2010LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho\u2010PI3K, phospho\u2010AKT, phospho\u2010mTOR, and phospho\u2010eNOS were determined by western blotting analysis. 3\u2010Methyladenine (3\u2010MA) and rapamycin were used to determine the role of autophagy in oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI complex\u2010induced endothelial cell dysfunction. We showed that oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3\u2010II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K\/AKT\/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI complex\u2010induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3\u2010MA alone induced the endothelial injury. Our results suggested that oxLDL\/\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI\/anti\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2GPI complex inhibited endothelial autophagy via PI3K\/AKT\/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.\n                  <\/jats:p>","DOI":"10.1155\/2021\/6662225","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T18:20:07Z","timestamp":1623781207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Impaired Autophagy Induced by oxLDL\/\n                    <i>\u03b2<\/i>\n                    2GPI\/anti\u2010\n                    <i>\u03b2<\/i>\n                    2GPI Complex through PI3K\/AKT\/mTOR and eNOS Signaling Pathways Contributes to Endothelial Cell Dysfunction"],"prefix":"10.1155","volume":"2021","author":[{"given":"Guiting","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-8802","authenticated-orcid":false,"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-8285","authenticated-orcid":false,"given":"Wei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0106-z"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0169-2"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-1169"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1395114"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.09.001"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309374"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2983-9"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.018"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0287-8"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy007"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.01.043"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061279"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.08.019"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12616"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.04.029"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2018.05.011"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147322"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000490016"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu011"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.224899"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.229690"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12973"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.12.011"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401751"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.028"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2007.11.011"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.103"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0063-y"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203307084170"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2007.06.003"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-008-8096-8"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.02.002"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.020"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.11787"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-12-42"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.1.13883"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1159\/000493817"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12709"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.10.840"},{"key":"e_1_2_10_41_2","first-page":"223","article-title":"The oxLDL\/\u03b22GPI\/anti-\u03b22GPI antibody complex induces apoptosis of human umbilical vein endothelial cells by promoting the production of reactive oxygen species","volume":"35","author":"Chen Y.","year":"2019","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0092"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3805"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.05.017"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303804"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303805"},{"key":"e_1_2_10_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23112912"},{"key":"e_1_2_10_48_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796697"},{"key":"e_1_2_10_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282f56bb7"},{"key":"e_1_2_10_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.02.020"},{"key":"e_1_2_10_51_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2840437"},{"key":"e_1_2_10_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.21376"},{"key":"e_1_2_10_53_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.9099"},{"key":"e_1_2_10_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.03.007"},{"key":"e_1_2_10_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2272"},{"key":"e_1_2_10_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02737-x"},{"key":"e_1_2_10_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200524408"},{"key":"e_1_2_10_58_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004373"},{"key":"e_1_2_10_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040880"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6662225.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6662225.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/6662225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T14:23:57Z","timestamp":1723040637000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/6662225"}},"subtitle":[],"editor":[{"given":"Ana","family":"Lloret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/6662225"],"URL":"https:\/\/doi.org\/10.1155\/2021\/6662225","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6662225"}}