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CAVD has several risk factors such as age and dyslipidemia. Vitamin K was shown to inhibit vascular calcification in mice and valvular calcification in patients with CAVD. We studied the effect of menaquinone 4 (MK4\/vitamin K2) on valvular calcification in the hypercholesterolemic mouse model of CAVD.<jats:italic>LDLr<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>ApoB<\/jats:italic><jats:sup><jats:italic>100\/100<\/jats:italic><\/jats:sup>male mice were fed with a Western diet for 5\u00a0months, with (n\u2009=\u200910) or without (n\u2009=\u200910) added 0.2\u00a0mg\/g MK4. Body weight gain was followed weekly. Morphology of aortic valves and liver was assessed with immunohistochemistry. Plasma cholesterol levels and cytokines from hepatic tissue were assessed in the end of the study. Hepatic gene expression of lipid metabolism regulating genes were assessed after 18\u00a0h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic<jats:italic>LDLr<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup><jats:italic>ApoB<\/jats:italic><jats:sup><jats:italic>100\/100<\/jats:italic><\/jats:sup>mice. The MK4-containing WD diet increased plasma levels of LDL and triglycerides, hepatic steatosis, and mRNA expression of genes required for triglyceride and cholesterol synthesis. MK4 diminished levels of several cytokines and chemokines in liver, including IL-6, TNF\u03b1 and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.<\/jats:p>","DOI":"10.1038\/s41598-021-82724-0","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T11:08:10Z","timestamp":1612436890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice"],"prefix":"10.1038","volume":"11","author":[{"given":"Jonna","family":"Weisell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Kaisa","family":"Ruotsalainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha","family":"N\u00e4p\u00e4nkangas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matti","family":"Jauhiainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaana","family":"Rys\u00e4","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"82724_CR1","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1093\/eurheartj\/ehx653","volume":"39","author":"FECM Peeters","year":"2018","unstructured":"Peeters, F. 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