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This study aimed to analyze whether orally administered RS inhibits the development of atherosclerosis, a chronic inflammation of the arteries. ApoE-deficient female mice were fed a normal or high-fat diet (HFD) with or without RS for 12 weeks. Immunohistochemical and mRNA analyses of atherosclerosis-related genes were performed. The effect of RS on the migration of RAW264.7 cells was also examined in vitro. RS administration suppressed the increase in blood total cholesterol and triglyceride levels. In the aorta of HFD-fed mice, RS reduced vascular smooth muscle cell proliferation, macrophage accumulation, and elevation of VCAM-1 and inhibited the reduction of Robo4. Increased mRNA levels of Vcam1, Mmp9, and Srebp1 in atherosclerotic areas of HFD-fed mice were also suppressed with RS. Moreover, RS directly inhibited the migration of RAW264.7 cells in vitro. Thus, in HFD-fed ApoE-deficient mice, oral administration of RS ameliorated abnormal lipid metabolism and reduced vascular endothelial inflammation and hyperpermeability, macrophage infiltration and accumulation, and smooth muscle cell proliferation in the arteries leading to atherosclerosis. These results suggest that RS is an effective functional food for the prevention of atherosclerosis.<\/jats:p>","DOI":"10.3390\/cells12222666","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:32:32Z","timestamp":1700476352000},"page":"2666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oral Administration of Rhamnan Sulfate from Monostroma nitidum Suppresses Atherosclerosis in ApoE-Deficient Mice Fed a High-Fat Diet"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-1569","authenticated-orcid":false,"given":"Masahiro","family":"Terasawa","sequence":"first","affiliation":[{"name":"Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-795X","authenticated-orcid":false,"given":"Liqing","family":"Zang","sequence":"additional","affiliation":[{"name":"Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Hiramoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4111-8262","authenticated-orcid":false,"given":"Yasuhito","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Mitsunaka","sequence":"additional","affiliation":[{"name":"Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Uchida","sequence":"additional","affiliation":[{"name":"Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Nishiura","sequence":"additional","affiliation":[{"name":"Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Konan Chemical Manufacturing Co., Ltd., Kitagomizuka, Kusu-cho, Yokkaichi 510-0103, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-4013","authenticated-orcid":false,"given":"Norihiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Minamitamagaki-cho, Suzuka 513-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1748-1716.2009.01964.x","article-title":"Endothelial dysfunction and vascular disease","volume":"196","author":"Vanhoutte","year":"2009","journal-title":"Acta Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bcp.2009.04.029","article-title":"Inflammatory cytokines in vascular dysfunction and vascular disease","volume":"78","author":"Sprague","year":"2009","journal-title":"Biochem. 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