Oslo, Norway, and East Brunswick, NJ—Smokers are at increased risk of cardiovascular disease, notes a press release from NattoPharma, although the precise mechanism at work is unknown. To this end,Cardiovascular Researchis publishing a new study that investigated the effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification, and examined vitamin K2 as a potential therapy.

The study was completed with the support of NattoPharma, as partner within the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant INTRICARE.

The researchers assessed vascular calcification of both smoking and non-smoking patients, and found that calcification was present more often in carotid plaques of smokers compared to non-smokers, confirming a higher atherosclerotic burden. The study noted that the difference was particularly profound “for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. Using induced human primary VSMC in vitro, nicotine increased osteogenic gene expression (Runx2, Osx, BSP and OPN), extracellular vesicle (EV) secretion and subsequently increased calcification.”

The pro-calcifying effects of nicotine were mediated by Nox5, which produces free radicals. The study also showed that Nox5 expression was higher in carotid arteries of smokers, and correlated with calcification levels in these vessels. Finally, the researchers found that pre-treatment of human VSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification.

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"In this study we show that smokers are at increased risk of cardiovascular events and that smoking impacts cardiovascular disease by increasing oxidative stress resulting in accelerated vascular calcification,” says Prof. Schurgers, Professor of Biochemistry of Vascular Calcification and Vice-Chair of Biochemistry at the Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, and corresponding author to this paper. “We show that vitamin K2, next to its well-known function as a cofactor in the activation of vitamin K-dependent proteins, also is an effective antioxidant capable of reducing oxidative stress.”

Dr. Hogne Vik, Chief Medical Officer with NattoPharma, added: “We have been working with Maastricht University for almost two decades validating the health benefits of vitamin K2, creating this category. Our work, in addition to others’, is building the necessary body of evidence required to convince regulatory bodies how essential vitamin K2 is for the betterment of global human health. And this new study adds to our current pursued argument that vitamin K2 can have a tremendous impact as a cardiovascular therapy – not only in healthy populations, but in patient or unhealthy populations, like nicotine users.”