{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:15:02Z","timestamp":1791148502620,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>An overproduction of oxidized low\u2010density lipoprotein (ox\u2010LDL) can lead to vascular endothelial dysfunction. Relaxin\u20102, a novel peptide hormone, exhibits various biological functions within the cardiovascular system. However, the effects of Relaxin\u20102 in atherosclerosis (AS) are underreported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aimed to investigate the regulatory role of Relaxin\u20102 in the endothelial function of human aortic endothelial cells (HAECs) upon ox\u2010LDL stimulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HAECs were stimulated with ox\u2010LDL (100\u2009mg\/l) and rhRelaxin\u20102 (25, 50\u2009nM) for 24\u2009h. Multiple techniques, including real\u2010time PCR, Western blot analysis, ELISA, and Calcein AM staining, were applied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with human recombinant (rh) Relaxin\u20102 decreased lectin\u2010like ox\u2010LDL receptor 1 (LOX\u20101), a primary receptor for ox\u2010LDL, in HAECs. rhRelaxin\u20102 also reduced the ox\u2010LDL\u2010induced expression of pro\u2010inflammatory mediators such as interleukin 6 (IL\u20106), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and monocyte chemoattractant protein\u20101 (MCP\u20101). Additionally, we observed increased expression of cyclooxygenase\u20102 (COX\u20102), prostaglandin E2 (PGE2), and high mobility group protein B1 (HMGB\u20101) in ox\u2010LDL\u2010challenged HAECs, which was diminished by rhRelaxin\u20102. Significantly, the heightened expression of intercellular cell adhesion molecule\u20101 (ICAM\u20101) and E\u2010selectin in ox\u2010LDL\u2010stimulated HAECs was mitigated by rhRelaxin\u20102. Consequently, rhRelaxin\u20102 alleviated the attachment of THP\u20101 cells to HAECs in a dose\u2010dependent manner. Mechanistically, we found that rhRelaxin\u20102 inhibited the expression of Egr\u20101, a central mediator of endothelial inflammation. Furthermore, overexpression of Egr\u20101 was found to negate the beneficial effects of rhRelaxin\u20102, suggesting that these effects are mediated by the suppression of Egr\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings propose a novel therapeutic approach with rhRelaxin\u20102 for patients with atherosclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.70007","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:06:55Z","timestamp":1744024015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Relaxin\u20102 mitigates the interaction between monocytes and endothelial cells by suppressing Egr\u20101"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2615-5012","authenticated-orcid":false,"given":"Jing","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Wuhan Prevention and Treatment Center for Occupational Diseases  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2020.12.013"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001052"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003392\u20108"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab173"},{"issue":"103","key":"e_1_2_11_6_1","first-page":"73","article-title":"Epigenetics in atherosclerosis: a clinical perspective","volume":"19","author":"Zhang BK","year":"2015","journal-title":"Discov Med"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.022367"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom8030080"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.07.004"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000955\u20107"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2021.3125"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwad005"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2023.107232"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25810"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.12.028"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.11.198"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202202108R"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.359"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.12.004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2024.04.016"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201063804\u2010z"},{"issue":"2","key":"e_1_2_11_22_1","first-page":"95","article-title":"Molecular mechanism on healing process of peptic ulcer","volume":"41","author":"Syam AF","year":"2009","journal-title":"Acta Med Indones"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753\u2010022\u201001778\u2010y"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11121886"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.11909\/j.issn.1671\u20135411.2020.05.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106224"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.9b00509"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010012\u20101375\u2010y"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00599"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392\u2010023\u201002305\u20101"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9090774"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010020\u201001926\u2010x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872\u2010023\u201003496\u20101"},{"issue":"11","key":"e_1_2_11_34_1","first-page":"467","article-title":"Relaxin\u20102 may suppress endometriosis by reducing fibrosis, scar formation, and inflammation","volume":"8","author":"Yoshino O","year":"2020","journal-title":"Biomedicine"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005675\u20106"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557516666160505115743"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114429"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2018.05.010"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5245308"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.02.024"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666180508100950"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.029272"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010020\u20100431\u20107"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181b91c9c"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124418"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000188710.04777.9e"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000145573.36113.8a"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.09.019"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1603"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad130"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2019.1573740"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-019-1333-6"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2018.01.002"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.70007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T13:50:29Z","timestamp":1757080229000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.70007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":53,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/fcp.70007"],"URL":"https:\/\/doi.org\/10.1111\/fcp.70007","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]},"assertion":[{"value":"2024-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"fcp.70007"}}