{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:31:16Z","timestamp":1772004676175,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"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":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The therapeutic effect of metformin (Met) on atherosclerosis was studied here. Effects of methionine and Met on the induction of inflammatory response and H<jats:sub>2<\/jats:sub>S expression in peritoneal macrophages were evaluated. Enzyme\u2010linked immunosorbent assay, immunohistochemistry assay, western blot, and quantitative reverse transcription polymerase chain reaction were conducted to observe the levels of cystathionine \u03b3\u2010lyase (CSE), DNA methyltransferases 1 (DNMT1), DNMT3a, DNMT3b, tumor necrosis factor (TNF\u2010 \u03b1), interleukin 1b (IL\u20101\u03b2), and hydrogen sulfide (H\n<jats:sub>2<\/jats:sub>S). Luciferase and bisulfite sequencing assays were also utilized to evaluate the CSE promoter activity as well as the methylation status of CSE in transfected cells. Methionine significantly elevated Hcy, TNF\u2010a, H\n<jats:sub>2<\/jats:sub>S, and IL\u20101\u03b2 expression while decreasing the level of CSE in C57BL\/6 mice. In contrary, co\u2010treatment with Methionine and Met reduced the detrimental effect of Methionine. Homocysteine (Hcy) decreased H\n<jats:sub>2<\/jats:sub>S expression while promoting the synthesis of IL\u20101\u03b2 and TNF\u2010\u03b1 in THP\u20101 and raw264.7 cells. Treatment of THP\u20101 and raw264.7 cells with methionine and Met reduced the activity of methionine in dose dependently. Moreover, Hcy increased the expression of DNMT and elevated the level of methylation in the CSE promoter, whereas the co\u2010treatment with methionine and Met attenuated the effects of Hcy. Methionine significantly decreased plasma level of CSE while increasing the severity of inflammatory responses and plasma level of Hcy, which in turn suppressed H\n<jats:sub>2<\/jats:sub>S synthesis and enhanced DNA hypermethylation of CSE promoter to promote the pathogenesis of atherosclerosis. In contrary, co\u2010treatment with methionine and Met reduced the detrimental effect of methionine.<\/jats:p>","DOI":"10.1002\/jcp.29112","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T04:29:30Z","timestamp":1563942570000},"page":"2102-2112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Administration of metformin alleviates atherosclerosis by promoting H2S production via regulating CSE expression"],"prefix":"10.1002","volume":"235","author":[{"given":"Xiaofeng","family":"Ma","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan University of South China  Hengyang Hunan China"},{"name":"Department of Cardiology, Affiliated Nanhua Hospital University of South China  Hengyang Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4459","authenticated-orcid":false,"given":"Zhisheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan University of South China  Hengyang Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Disease and Key Lab for Arteriosclerology of Hunan University of South China  Hengyang Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Beijing Hospital of Traditional Chinese Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21521"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.164970"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706186"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010006\u20100106\u20105"},{"key":"e_1_2_8_1_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010007\u20100011\u20108"},{"key":"e_1_2_8_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.367"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807974105"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38415.708634.F7"},{"key":"e_1_2_8_1_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2012.843"},{"key":"e_1_2_8_1_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5023"},{"key":"e_1_2_8_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.07.025"},{"key":"e_1_2_8_1_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_2_8_1_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1882"},{"key":"e_1_2_8_1_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000029784.15893.10"},{"key":"e_1_2_8_1_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12\u20100719"},{"key":"e_1_2_8_1_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000201938.78044.75"},{"issue":"23","key":"e_1_2_8_1_18_1","first-page":"5310","article-title":"Methylation of the androgen receptor promoter CpG island is associated with loss of androgen receptor expression in prostate cancer cells","volume":"58","author":"Jarrard D. 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