Micro-calcification formation detectable with Sodium [18F]Fluoride positron emission tomography and preventable with vitamin K2

Vascular calcification is recognized as an independent cardiovascular risk factor and as a marker for plaque vulnerability, alongside inflammation. Sodium [18F]Fluoride (Na[18F]F) positron emission tomography (PET) has been proposed as a superior imaging technique enabling the correct identification of micro-calcified plaque. Vitamin K—especially Menaquinone-7 (MK-7)—has been highly valued as a cost-effective method for delaying the progression of vascular calcification. Results of a study that assessed the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model have been published in Cells journal.

The authors tested the ability of Na[18F]F PET to detect small changes in plaque morphology in atherosclerotic mice, that were given either MK-7 supplementation, or Warfarin or Phylloquinone supplementation, or were maintained on the atherogenic diet. Vitamin K is a crucial cofactor in the post-translational modification of various proteins, including coagulation factors and matrix γ-carboxyglutamate protein (i.e., MGP), the latter of which is involved in the inhibition of ectopic calcification. Considering this mechanism of action, vitamin K has received the attention of several ongoing clinical trials. MK-7 thanks to its increased half-life in blood, which extends its uptake availability through extra-hepatic tissues, is one of the most used in preclinical and clinical trials.

The following knowledge has been gained by the researchers as an outcome of this trial: the Warfarin group presented spotty calcifications on the CT in the proximal aorta, and after the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications.

“As presented in this study, Na[18F]F PET has the potential to monitor plaque progression and treatment,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “The study revealed also that vitamin K2 supplementation might have a protective role against micro-calcification formation,  which is crucial for cardiovascular health,” she points out.

“This finding adds to the previously described list of the beneficial effects of vitamin K for cardiovascular health, which, in combination with ongoing clinical trials, may favor the increase in the recommended daily dose of vitamin K or its introduction in clinical practice,” Dr. Maresz emphasizes.

References:

Florea A, Sigl JP, Morgenroth A, Vogg A, Sahnoun S, Winz OH, Bucerius J, Schurgers LJ, Mottaghy FM. Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment. Cells. 2021 Jan 30;10(2):275. doi: 10.3390/cells10020275. PMID: 33573188; PMCID: PMC7911917.

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