Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation

Anna Kieronska-Rudek; Agnieszka Kij; Anna Bar; Anna Kurpinska; Tasnim Mohaissen; Marek Grosicki; Marta Stojak; Magdalena Sternak; Elżbieta Buczek; Bartosz Proniewski; Kamil Kuś; Joanna Suraj-Prazmowska; Agnieszka Panek; Monika Pietrowska; Szczepan Zapotoczny; Catherine M. Shanahan; Csaba Szabo; Stefan Chlopicki

doi:10.1007/s11357-024-01225-w

Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation

Anna Kieronska-Rudek, Agnieszka Kij, Anna Bar, Anna Kurpinska, Tasnim Mohaissen, Marek Grosicki, Marta Stojak, Magdalena Sternak, Elżbieta Buczek, Bartosz Proniewski, Kamil Kuś, Joanna Suraj-Prazmowska, Agnieszka Panek, Monika Pietrowska, Szczepan Zapotoczny, Catherine M. Shanahan, Csaba Szabo, Stefan Chlopicki^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR^−/− mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR^−/− mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.

Original language	English
Pages (from-to)	4909-4935
Number of pages	27
Journal	GeroScience
Volume	46
Issue number	5
DOIs	https://doi.org/10.1007/s11357-024-01225-w
Publication status	Published - Oct 2024

Keywords

Anti-inflammatory
Anti-senescence
DNA damage
Vasoprotection
Vitamin K

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11357-024-01225-w

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Kieronska-Rudek, A., Kij, A., Bar, A., Kurpinska, A., Mohaissen, T., Grosicki, M., Stojak, M., Sternak, M., Buczek, E., Proniewski, B., Kuś, K., Suraj-Prazmowska, J., Panek, A., Pietrowska, M., Zapotoczny, S., Shanahan, C. M., Szabo, C., & Chlopicki, S. (2024). Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation. GeroScience, 46(5), 4909-4935. https://doi.org/10.1007/s11357-024-01225-w

@article{e177eace7a2440fcb5dea054190a7d44,

title = "Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation",

abstract = "Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR−/− mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR−/− mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.",

keywords = "Anti-inflammatory, Anti-senescence, DNA damage, Vasoprotection, Vitamin K",

author = "Anna Kieronska-Rudek and Agnieszka Kij and Anna Bar and Anna Kurpinska and Tasnim Mohaissen and Marek Grosicki and Marta Stojak and Magdalena Sternak and El{\.z}bieta Buczek and Bartosz Proniewski and Kamil Ku{\'s} and Joanna Suraj-Prazmowska and Agnieszka Panek and Monika Pietrowska and Szczepan Zapotoczny and Shanahan, {Catherine M.} and Csaba Szabo and Stefan Chlopicki",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = oct,

doi = "10.1007/s11357-024-01225-w",

language = "English",

volume = "46",

pages = "4909--4935",

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Kieronska-Rudek, A, Kij, A, Bar, A, Kurpinska, A, Mohaissen, T, Grosicki, M, Stojak, M, Sternak, M, Buczek, E, Proniewski, B, Kuś, K, Suraj-Prazmowska, J, Panek, A, Pietrowska, M, Zapotoczny, S, Shanahan, CM, Szabo, C & Chlopicki, S 2024, 'Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation', GeroScience, vol. 46, no. 5, pp. 4909-4935. https://doi.org/10.1007/s11357-024-01225-w

TY - JOUR

T1 - Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation

AU - Kieronska-Rudek, Anna

AU - Kij, Agnieszka

AU - Bar, Anna

AU - Kurpinska, Anna

AU - Mohaissen, Tasnim

AU - Grosicki, Marek

AU - Stojak, Marta

AU - Sternak, Magdalena

AU - Buczek, Elżbieta

AU - Proniewski, Bartosz

AU - Kuś, Kamil

AU - Suraj-Prazmowska, Joanna

AU - Panek, Agnieszka

AU - Pietrowska, Monika

AU - Zapotoczny, Szczepan

AU - Shanahan, Catherine M.

AU - Szabo, Csaba

AU - Chlopicki, Stefan

PY - 2024/10

Y1 - 2024/10

N2 - Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR−/− mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR−/− mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.

AB - Phylloquinon (PK) and menaquinones (MK) are both naturally occurring compounds belonging to vitamin K group. Present study aimed to comprehensively analyze the influence of PK in several models of vascular dysfunction to determine whether PK has vasoprotective properties, similar to those previously described for MK. Effects of PK and MK on endothelial dysfunction were studied in ApoE/LDLR−/− mice in vivo, in the isolated aorta incubated with TNF, and in vascular cells as regard inflammation and cell senescence (including replicative and stress-induced models of senescence). Moreover, the vascular conversion of exogenous vitamins to endogenous MK-4 was analyzed. PK, as well as MK, given for 8 weeks in diet (10 mg/kg) resulted in comparable improvement in endothelial function in the ApoE/LDLR−/− mice. Similarly, PK and MK prevented TNF-induced impairment of endothelium-dependent vasorelaxation in the isolated aorta. In in vitro studies in endothelial and vascular smooth muscle cells, we identified that both PK and MK displayed anti-senescence effects via decreasing DNA damage while in endothelial cells anti-inflammatory activity was ascribed to the modulation of NFκB activation. The activity of PK and MK was comparable in terms of their effect on senescence and inflammation. Presence of endogenous synthesis of MK-4 from PK in aorta and endothelial and smooth muscle cells suggests a possible involvement of MK in vascular effects of PK. In conclusion, PK and MK display comparable vasoprotective effects, which may be ascribed, at least in part, to the inhibition of cell senescence and inflammation. The vasoprotective effect of PK in the vessel wall can be related to the direct effects of PK, as well as to the action of MK formed from PK in the vascular wall.

KW - Anti-inflammatory

KW - Anti-senescence

KW - DNA damage

KW - Vasoprotection

KW - Vitamin K

UR - http://www.scopus.com/inward/record.url?scp=85198109789&partnerID=8YFLogxK

U2 - 10.1007/s11357-024-01225-w

DO - 10.1007/s11357-024-01225-w

M3 - Article

AN - SCOPUS:85198109789

SN - 2509-2715

VL - 46

SP - 4909

EP - 4935

JO - GeroScience

JF - GeroScience

IS - 5

ER -

Phylloquinone improves endothelial function, inhibits cellular senescence, and vascular inflammation

Abstract

Keywords

UN SDGs

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