Authors
Elena Repges, Adem Aksoy, Katrin J Czogalla-Nitsche, Andreas Zietzer, Cornelius Müller, Johannes Oldenburg, Sebastian Zimmer, Georg Nickenig, Vedat Tiyerili, Muntadher Al Zaidi
Published in
Scientific reports. Volume 16. Issue 1. Jun 19, 2026. Epub Jun 19, 2026.
Abstract
Vitamin K is classically known for hepatic γ-carboxylation via VKORC1, yet accumulating evidence suggests broader redox-regulatory roles. Here, we characterize the VKORC1 paralogue VKORC1L1 as an anti-oxidative enzyme that couples the vitamin K cycle to ferroptosis defense in the endothelium. In human coronary artery endothelial cells (HCAEC), menaquinone-7 (Vitamin K2, MK-7) increased viability and attenuated RSL3-induced lipid peroxidation, ferroptosis, and NF-κB-dependent inflammatory activation. In vivo, a MK-7 enriched diet accelerated reendothelialization after electric carotid injury in C57BL/6J mice without altering hemostasis. Silencing VKORC1L1, but not the coagulation-linked VKORC1, diminished HCAEC proliferation, raised reactive oxygen species, and triggered NF-κB activation. Importantly, MK-7 failed to rescue these effects in VKORC1L1-deficient cells, supporting a functional requirement for VKORC1L1 in vitamin K-mediated cytoprotection. Transcriptomics of VKORC1L1-deficient cells revealed a lipid peroxide/NF-κB/TNF pathway that amplified oxidative inflammation. This signaling axis was blocked by the lipid-radical scavenger ferrostatin-1 or by inhibiting TNF shedding. Collectively, these data identify VKORC1L1 as a redox-responsive component of the endothelial vitamin K cycle that limits lipid peroxides, suppresses ferroptosis, restrains TNF-driven inflammation, and promotes vascular repair.
PMID:
42321255
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.
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