{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:05:44Z","timestamp":1790849144020,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cardiovascular complications are the major causes of the mortality and morbidities in diabetic patients. The diabetic patients have an increased risk of developing atherosclerosis, which could lead to heart attack and stroke. Glucagon\u2010like peptide 1 (GLP\u20101) receptor agonists are a class of potent anti\u2010glycemic agents to treat diabetes. Recently, several GLP\u20101 receptor agonists have been found to have cardiovascular benefit independent of their glucose lowing ability. Liraglutide is one of clinically approved effective GLP\u20101 receptor agonists. In this study, we explored the molecular mechanism of Liraglutide against oxidized low\u2010density lipoprotein (ox\u2010LDL) in cultured endothelial cells. Our data show that Liraglutide treatment ameliorates ox\u2010LDL caused reduction of the transcriptional factor KLF2. In the same experiment, Liraglutide also rescues ox\u2010LDL induced reduction of mitogen\u2010activated protein kinase (MAPK) kinase extracellular signal regulated kinase 5 (ERK5) phosphorylation, and blockage of ERK5 activity by its inhibitor XMD8\u201092 abolishes the protection of Liraglutide on KLF2 expression. These facts suggest that the action of Liraglutide on endothelial KLF2 is dependent on ERK5. Liraglutide also recovers ox\u2010LDL caused reduction of endothelial tight junctions protein Occludin and ameliorates ox\u2010LDL induced endothelial monolayer permeability increase. On the other hand, Liraglutide inhibits ox\u2010LDL induced expression of vascular adhesion molecules (E\u2010selectin and vascular cell adhesion molecule 1), and prevents ox\u2010LDL induced attachment of monocytes adhesion to endothelial cells. Moreover, Liraglutide mitigates ox\u2010LDL triggered reduction of endothelial nitric oxide synthase (eNOS) expression and NO release. Collectively, our study provides multiple facets of the mechanisms that Liraglutide is a protective agent in endothelial cells and has the potential implication in therapeutic usage of vascular complication in diabetes patients. \u00a9 2019 IUBMB Life, 71(9):1347\u20131354, 2019<\/jats:p>","DOI":"10.1002\/iub.2046","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T11:48:42Z","timestamp":1554896922000},"page":"1347-1354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["The GLP\u20101 receptor agonist liraglutide protects against oxidized LDL\u2010induced endothelial inflammation and dysfunction via KLF2"],"prefix":"10.1002","volume":"71","author":[{"given":"Wen","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Cardiology West China Hospital of Sichuan University  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jiajiang Rehabilitation Hospital  Leshan Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengke","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Cardiology Chengdu Fifth People's Hospital  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3206-9937","authenticated-orcid":false,"given":"Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology West China Hospital of Sichuan University  Chengdu Sichuan People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"World Health Organization. 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