{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:23:14Z","timestamp":1793719394323,"version":"4.6.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gout is a multifaceted inflammatory disease involving vascular impairments induced by hyperuricemia. Experiments using human umbilical vein endothelial cells treated with uric acid (UA), monosodium urate (MSU), or serum from gout patients showed increased expression of pro\u2010inflammatory genes (ie, VCAM1, ICAM1, CYR61, CCNA1, and E2F1) with attendant increase in monocyte adhesion. Mechanistically, UA\u2010 or MSU\u2010induced SREBP2 expression and its transcriptional activity. RNA sequencing analysis and real\u2010time PCR showed the induction of YAP signaling and pro\u2010inflammatory pathways in HUVECs transfected with adenovirus\u2010SREBP2. The SREBP2 knockdown by siRNA partially abolished UA\u2010 or MSU\u2010induced YAP activity, pro\u2010inflammatory gene expression, and monocytes adhesion. Vascular intima from transgenic mice overexpressing SREBP2 in endothelium or mice with hyperuricemia exhibited activated YAP signaling and increased expression of pro\u2010inflammatory genes. Betulin, an SREBP pharmacological inhibitor, attenuated the UA\u2010, MSU\u2010, or gout serum\u2010induced endothelial cell inflammation and dysfunction. In the human study, endothelial cell function, assessed by EndoPAT, was negatively correlated with serum UA level among gouty patients and healthy controls. Collectively, UA or MSU causes endothelial dysfunction via SREBP2 transactivation of YAP. Betulin inhibition of SREBP2 may restrain gout\u2010induced endothelial dysfunction.<\/jats:p>","DOI":"10.1096\/fj.202100337r","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T03:56:17Z","timestamp":1620791777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Gout\u2010induced endothelial impairment: The role of SREBP2 transactivation of YAP"],"prefix":"10.1096","volume":"35","author":[{"given":"Zunlan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of General Medicine Henan Provincial People\u2019s Hospital, People's Hospital of Zhengzhou University Zhengzhou Henan China"},{"name":"Division of Cardiology, Department of Medicine University of California, San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshuai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of General Medicine Henan Provincial People\u2019s Hospital, People's Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine University of California, San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Medicine Henan Provincial People\u2019s Hospital, People's Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Henan Provincial People\u2019s Hospital, People's Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Y.\u2010J.","family":"Shyy","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine University of California, San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-1826","authenticated-orcid":false,"given":"Ming","family":"He","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine University of California, San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Medicine Henan Provincial People\u2019s Hospital, People's Hospital of Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30221-6"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-018-9604-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.10.007"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.07.013"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400525"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050572"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2012.747677"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2014.08.006"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000107"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002714"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013675"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618773114"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2014"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.044"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.87"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613121113"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20602"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14262"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.12.004"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600106"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39254"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1602907"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.91"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-017-0050-9"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.98"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2491"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161205774913255"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-014-1057-1"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1012-3"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179426"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-013-8402-y"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2148"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.03.250"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2936"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.107"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00200"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/584189"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24020355"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.46"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.11.044"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202100337R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202100337R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202100337R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T18:47:17Z","timestamp":1764355637000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202100337R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1096\/fj.202100337R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202100337r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"2021-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21613"}}