University of Oulu

Weisell, J., Ruotsalainen, AK., Näpänkangas, J. et al. Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice. Sci Rep 11, 3014 (2021).

Menaquinone 4 increases plasma lipid levels in hypercholesterolemic mice

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Author: Weisell, Jonna1; Ruotsalainen, Anna-Kaisa2; Näpänkangas, Juha3;
Organizations: 1School of Pharmacy, University of Eastern Finland, POB 1627, 70211, Kuopio, Finland
2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
3Department of Pathology, University of Oulu, Oulu University Hospital, Oulu, Finland
4Minerva Foundation Institute for Medical Research, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-04-29


In calcific aortic valve disease (CAVD) progressive valvular calcification causes aortic valve dysfunction. 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. LDLr−/− ApoB100/100 male mice were fed with a Western diet for 5 months, with (n = 10) or without (n = 10) added 0.2 mg/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 h diet. MK4 exacerbated the lipoprotein lipid profile without affecting aortic valve morphology in hypercholesterolemic LDLr−/− ApoB100/100 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, TNFα and MCP1, as measured by hepatic cytokine array. Consequently, MK4 may exert non-beneficial effects on circulating lipid levels, especially in hypercholesterolemic individuals.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 11
Issue: 1
Article number: 3014
DOI: 10.1038/s41598-021-82724-0
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by the Academy of Finland (Grant Numbers 276747, 284504 and 312611); the Finnish Cultural Foundation and the Finnish Foundation of Cardiovascular Research.
Copyright information: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit