Non-Canonical Role of MK-7 in Vascular Smooth Muscle Cells—Promoting Energy and Inhibiting of Oxidative Stress †
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands
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Author to whom correspondence should be addressed.
†
Presented at the 2nd International Electronic Conference on Nutrients, 15–31 March 2022; Available online: https://iecn2022.sciforum.net/ .
Biol. Life Sci. Forum 2022, 12(1), 3; https://doi.org/10.3390/IECN2022-12401
Published: 14 March 2022
(This article belongs to the Proceedings of The 2nd International Electronic Conference on Nutrients)
Abstract
:Background: The sequential processes that lead to pathological cardiovascular remodeling are unclear. From the multiple components that constitute the cardiovascular system, it is believed that vascular smooth muscle cells (SMCs) play a central role. SMCs have the ability to differentiate into a proliferative and migratory phenotype which supports vessel homeostasis. These synthetic SMCs display increased oxidative stress, secrete extracellular vesicles, and promote vascular calcification. SMC driven calcification is regulated by vitamin K-dependent matrix Gla protein (MGP). Since vitamin K promotes energy to bacteria, and vitamin K can scavenge free radicals and reduce oxidative stress, we reasoned that vitamin K can have non-canonical functions to decrease vascular calcification. Aim: We investigated the potential of vitamin K to reduce oxidative stress and support ATP synthesis in SMCs. Methods: Primary SMCs were cultured in M199 medium containing 20% FBS and 1% P/S. Warfarin (vitamin K antagonist; 10 microM) and MK-7 (10 microM) were added and ATP (luminescence), oxidative stress (DCFDA) and extracellular vesicles (EV: CD63-CD81-PE bead-assay) were measured. Results: We show that SMCs take up MK-7 very efficiently. Interference with vitamin K metabolism using warfarin resulted in increased intracellular oxidative stress (4 fold; p < 0.005) and EV release (2.5 fold; p < 0.01). The addition of MK-7 counteracts intracellular oxidative stress, both under normal conditions (2 fold; p < 0.05), as well as under warfarin-induced oxidative stress conditions (4 fold; p < 0.001). Additionally, chronic hypoxia induced by the HIF1a stabilizing cobalt chloride induced increased oxidative stress (2.5 fold; p < 0.01), and MK-7 could counteract oxidative stress, indicative for improved mitochondrial activity. Finally, MK-7 increased ATP production as compared to vehicle (15%; p < 0.05), even in the presence of warfarin. Conclusion: Our experiments show that in primary human SMCs, MK-7 lowers oxidative stress and EV release and increases ATP production. This pathway points to a non-canonical role of MK-7 in the prevention of vascular calcification, unrelated to its canonical role as a cofactor for the posttranslational modification of MGP.
Supplementary Materials
The conference poster is available at https://www.mdpi.com/article/10.3390/IECN2022-12401/s1.
Author Contributions
Author Contributions: Conceptualization, A.C.A. and L.J.S.; methodology, A.C.A.; formal analysis, A.C.A.; investigation, A.C.A. and L.J.S.; writing—original draft preparation, A.C.A. and L.J.S.; writing—review and editing, A.C.A. and L.J.S.; visualization, A.C.A. and L.J.S.; supervision, A.C.A. and L.J.S.; project administration, L.J.S.; funding acquisition, L.J.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Nattopharma (Oslo, Norway).
Institutional Review Board Statement
Collection, storage, and use of tissue and human aortic samples were performed in agreement with the Dutch Code for Proper Secondary Use of Human Tissue. No experiments on human or animal material requiring ethical approval were performed in this study.
Informed Consent Statement
Collection, storage, and use of tissue and human aortic samples were performed in agreement with the Dutch Code for Proper Secondary Use of Human Tissue.
Data Availability Statement
Data are available upon reasonable request from the corresponding author.
Conflicts of Interest
L.J.S. reports research funding from Nattopharma, related to this work. L.J.S. reports research funding from Bayer, Boehringer Ingelheim, and IDS outside this work. A.C.A. reports no conflict of interest.
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MDPI and ACS Style
Akbulut, A.C.; Schurgers, L.J. Non-Canonical Role of MK-7 in Vascular Smooth Muscle Cells—Promoting Energy and Inhibiting of Oxidative Stress. Biol. Life Sci. Forum 2022, 12, 3. https://doi.org/10.3390/IECN2022-12401
AMA Style
Akbulut AC, Schurgers LJ. Non-Canonical Role of MK-7 in Vascular Smooth Muscle Cells—Promoting Energy and Inhibiting of Oxidative Stress. Biology and Life Sciences Forum. 2022; 12(1):3. https://doi.org/10.3390/IECN2022-12401
Chicago/Turabian StyleAkbulut, Asim Cengiz, and Leon J. Schurgers. 2022. "Non-Canonical Role of MK-7 in Vascular Smooth Muscle Cells—Promoting Energy and Inhibiting of Oxidative Stress" Biology and Life Sciences Forum 12, no. 1: 3. https://doi.org/10.3390/IECN2022-12401
