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Low phylloquinone intake deteriorates endothelial function in normolipidemic and dyslipidaemic mice.

Title: Low phylloquinone intake deteriorates endothelial function in normolipidemic and dyslipidaemic mice.
Authors: Kij A; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Kieronska-Rudek A; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland; Jagiellonian University Medical College, Krakow, Poland.; Bar A; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Czyzynska-Cichon I; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Strus M; Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Krakow, Poland.; Kozien L; Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Krakow, Poland.; Wiecek G; Jagiellonian University Medical College, Department of Bacteriology, Microbial Ecology and Parasitology, Krakow, Poland.; Zeber-Lubecka N; Centre of Postgraduate Medical Education Department of Gastroenterology, Hepatology and Clinical Oncology, Warszawa, Poland; Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warszawa, Poland.; Kulecka M; Centre of Postgraduate Medical Education Department of Gastroenterology, Hepatology and Clinical Oncology, Warszawa, Poland; Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warszawa, Poland.; Kwiatkowski G; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Przyborowski K; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Mohaissen T; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland; University of Copenhagen, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Copenhagen, Denmark.; Sternak M; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Buczek E; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Zakrzewska A; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Proniewski B; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Kus K; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland.; Franczyk-Zarow M; University of Agriculture in Krakow, Faculty of Food Technology, Department of Human Nutrition and Dietetics, Krakow, Poland.; Kostogrys RB; University of Agriculture in Krakow, Faculty of Food Technology, Department of Human Nutrition and Dietetics, Krakow, Poland.; Pieterman EJ; The Netherlands Organization of Applied Scientific Research (TNO), Metabolic Health Research, Gaubius Laboratory, Leiden, The Netherlands.; Princen HMG; The Netherlands Organization of Applied Scientific Research (TNO), Metabolic Health Research, Gaubius Laboratory, Leiden, The Netherlands.; Chlopicki S; Jagiellonian University, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland; Jagiellonian University Medical College, Krakow, Poland. Electronic address: stefan.chlopicki@jcet.eu.
Source: The Journal of nutritional biochemistry [J Nutr Biochem] 2025 Jun; Vol. 140, pp. 109867. Date of Electronic Publication: 2025 Feb 18.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Science Country of Publication: United States NLM ID: 9010081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4847 (Electronic) Linking ISSN: 09552863 NLM ISO Abbreviation: J Nutr Biochem Subsets: MEDLINE
Imprint Name(s): Publication: : New York, NY : Elsevier Science; Original Publication: Stoneham, MA, USA : Butterworths, c1990-
MeSH Terms: Endothelium, Vascular*/physiopathology ; Endothelium, Vascular*/drug effects ; Endothelium, Vascular*/metabolism ; Vitamin K 1*/administration & dosage ; Vitamin K 1*/blood ; Dyslipidemias*/physiopathology ; Dyslipidemias*/metabolism; Vitamin K 2/analogs & derivatives ; Vitamin K 2/metabolism ; Liver/metabolism ; Vasodilation/drug effects ; Aorta/metabolism ; Animals ; Male ; Mice, Inbred C57BL ; Mice ; Gastrointestinal Microbiome ; Dietary Supplements
Abstract: While the plasma phylloquinone (PK) concentration is inversely correlated with cardiovascular risk, the involvement of PK in regulating endothelial function has not been directly investigated. Therefore, in this study we assessed the effects of short-term treatment with PK-deficient diets (5-10 weeks) on endothelial function in normolipidemic 14-week-old male C57BL/6JCmd mice and age-matched dyslipidaemic male E3L.CETP mice. Our results show that in normolipidemic mice dietary PK deficiency was associated with a marked reduction of PK levels in the plasma and liver (liquid chromatography-mass spectrometry measurements) and with impaired endothelium-dependent vasodilation assessed in vivo by magnetic resonance imaging (MRI). Dietary PK deficiency-induced endothelial dysfunction was fully reversed by PK supplementation. In dyslipidaemic E3L.CETP mice, dietary PK deficiency exacerbated preexisting endothelial dysfunction. Furthermore, dietary PK deficiency decreased menaquinone-4 (MK-4) levels in the aorta but did not affect blood coagulation (calibrated automated thrombography), microbiota composition (culturing and next-generation sequencing), and gut menaquinone production. In conclusion, our study demonstrated for the first time that sufficient dietary PK intake supports endothelial function in normolipidemic and dyslipidaemic mice indicating nutritional significance of dietary PK in the maintenance of endothelial function in humans.; (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Cardiovascular risk; Dietary PK deficiency; Endothelial function; MRI; Phylloquinone
Substance Nomenclature: 84-80-0 (Vitamin K 1); 11032-49-8 (Vitamin K 2)
Entry Date(s): Date Created: 20250220 Date Completed: 20250420 Latest Revision: 20250420
Update Code: 20260130
DOI: 10.1016/j.jnutbio.2025.109867
PMID: 39978646
Database: MEDLINE

Journal Article