{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:44:49Z","timestamp":1789062289917,"version":"build-2803163510"},"reference-count":0,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p>Background\/Aims: Recently, studies have shown that interleukin-37 (IL-37) is involved in atherosclerosis-related diseases. However, the regulatory mechanisms of IL-37 in atherosclerosis remain unknown. This study aims to determine the role of IL-37 in atherosclerosis and to investigate the underlying mechanisms involved. Methods: IL-37 expression in human atherosclerotic plaques was detected by immunohistochemical staining and real-time reverse transcription polymerase chain reaction (RT-PCR). Oil Red O staining was used to measure the size of plaques. Cell apoptosis in vitro and in vivo was tested by flow cytometric analysis and terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) staining, respectively. Protein expression levels of IL-37, IL-18R\u03b1 and p-Smad3 were measured by Weston blotting. Results: Immunohistochemical staining revealed that IL-37 was highly expressed in human atherosclerotic plaques. Intracellular cytokine staining revealed that infiltrated CD4+ T lymphocytes and vascular smooth muscle cells (VSMCs), but not macrophages, were the major sources of IL-37. Mice that overexpressed IL-37 exhibited significant improvements in their atherosclerotic burden, as demonstrated by reduced plaque size, increased collagen levels, and reduced numbers of apoptotic cells in vivo. Subsequently, mechanistic studies showed that IL-37 played an anti-atherosclerotic role, at least partially, through reducing inflammation by promoting the differentiation of the T helper cell anti-inflammatory phenotype, and through increasing plaque stability by decreasing matrix metalloproteinase (MMP)-2\/13-mediated degradation of collagen and inhibiting VSMCs apoptosis. Conclusion: IL-37 may be a novel potential therapeutic target in patients with atherosclerotic heart disease.<\/jats:p>","DOI":"10.1159\/000487344","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T22:01:33Z","timestamp":1518559293000},"page":"1034-1050","source":"Crossref","is-referenced-by-count":38,"title":["Transgenic Overexpression of IL-37 Protects Against Atherosclerosis and Strengthens Plaque Stability"],"prefix":"10.1159","volume":"45","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaolin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengshuai","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianguo","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2018,2,7]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/487344","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/487344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:42:30Z","timestamp":1745426550000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000487344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,2,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000487344","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5882485","asserted-by":"subject"}]},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}