Vitamin K2-MK-7 improves nitric oxide-dependent endothelial function in ApoE/LDLR−/− mice

Anna Bar , Kamil Kus , Angelika Manterys , Bartosz Proniewski , Magdalena Sternak , Kamil Przyborowski , Martijn Moorlag , Barbara Sitek , Brygida Marczyk , Agnieszka Jasztal , Tomasz Skórka , Magdalena Franczyk-Żarów , Renata Kostogrys , Stefan Chlopicki

Abstract

Although, vitamin K2 displays vasoprotective effects, it is still not known whether K2 treatment improves endothelial function. In ApoE/LDLR−/− mice at the stage prior to atherosclerosis development, four-week treatment with K2-MK-7, given at a low dose (0.05 mg/kg), improved acetylcholine- and flow-induced, endothelium-dependent vasodilation in aorta or in femoral artery, as assessed by MRI in vivo. This effect was associated with an increased NO production, as evidenced by EPR measurements in ex vivo aorta. Treatment with higher doses of K2-MK-7 (0.5; 5 mg/kg) resulted in a dose-dependent increase in plasma K2-MK-7 and K2-MK-4 concentration, without further improvement in endothelial function. In ApoE/LDLR−/− mice with developed atherosclerotic plaques, treatment with a low (0.03 mg/kg) or high (10 mg/kg) dose of K2-MK-7 resulted in a similar degree of endothelium-dependent vasodilation improvement and increase in plasma nitrate concentration, what was not associated with changes in thrombin generation as measured by CAT. Both doses of K2-MK-7 also reduced media thickness in the brachiocephalic artery, but did not modify atherosclerotic plaque size. In conclusion, K2-MK-7 improves NO-dependent endothelial function in ApoE/LDLR−/− mice. This study, identifies the endothelial profile of the pharmacological activity of vitamin K2, which has not been previously described.
Author Anna Bar
Anna Bar,,
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, Kamil Kus
Kamil Kus,,
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, Angelika Manterys (FoFT / DoHN)
Angelika Manterys,,
- Department of Human Nutrition
, Bartosz Proniewski
Bartosz Proniewski,,
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, Magdalena Sternak
Magdalena Sternak,,
-
, Kamil Przyborowski
Kamil Przyborowski,,
-
, Martijn Moorlag
Martijn Moorlag,,
-
, Barbara Sitek
Barbara Sitek,,
-
, Brygida Marczyk
Brygida Marczyk,,
-
, Agnieszka Jasztal
Agnieszka Jasztal,,
-
et al.`
Journal seriesVascular Pharmacology, ISSN 1537-1891, e-ISSN 1879-3649, (N/A 100 pkt)
Issue year2019
Vol122-123
No106581
Pages1-13
Publication size in sheets0.6
Keywords in EnglishEndothelial function, Atherosclerosis, MRI, Menaquinone-7
ASJC Classification1313 Molecular Medicine; 1314 Physiology; 3004 Pharmacology
DOIDOI:10.1016/j.vph.2019.106581
URL https://www.sciencedirect.com/science/article/pii/S153718911930031X/pdfft?md5=0d83859cdacbc81216f811074b119e3e&pid=1-s2.0-S153718911930031X-main.pdf
Languageen angielski
Score (nominal)100
Score sourcejournalList
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.079; WoS Impact Factor: 2018 = 3.33 (2) - 2018=3.471 (5)
Citation count*
Additional fields
FinansowanieThis work was supported by Polish National Science Centre grants: OPUS Grant No. 2018/29/B/NZ7/01684, PRELUDIUM Grant No.2016/23/N/NZ5/00595 and partially by Kaydence Pharma.
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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