Inactivation of a vitamin K-dependent protein may contribute to the development of varicose veins, says a new study that highlights the role of supplementation for improving vascular health.
The study, published in the Journal of Vascular Research, indicates that inadequate levels of vitamin K may reduce the activity of the matrix GLA protein (MGP) to reduce vascular proliferation and mineralisation, thereby stopping the development of varicosis. Varicose veins have an estimated prevalence of between five to 30 per cent in the adult population, with women three times more likely to develop varicose veins than men. The exact mechanisms behind varicose vein development are not clear, although several risk factors are known to be involved, including age, obesity, physical activity, standing occupations, genetic predispositions, multiple pregnancies and connective tissue abnormalities. The new study reports that MGP activity may also play an important role in the development of these types of veins.
"Defects in the vein wall are indicated in varicosis, with a central role for the vitamin-K dependent protein MGP," explained study co-author Leon Schurgers from the University of Maastricht. "MGP is important in relation to the health of the entire cardiovascular system. Previous studies from our group demonstrated the importance of MGP and vitamin K for the arterial vessel wall, and now we show that MGP and vitamin K could play a significant role in varicose veins," he added. There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90 per cent of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10 per cent of Western vitamin K consumption and can be synthesised in the gut by microflora. Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7.
MK-4 is distinct from other MKs because it is not a major constituent of the spectrum of MKs produced by gut microflora, but can be derived from K1 in vivo. A synthetic form of vitamin K, known as K3, does exist but is not recommended for human consumption. The researchers, led by Chrystelle Cario-Toumaniantz from INSERM (U533) and the University of Nantes, compared healthy veins from 36 male patients (age range 30 to 83) and varicose veins from 50 male patients (age range 40 to 81). Inactive MGP was identified by the researchers as a key player in the development of varicosis, and since vitamin K is necessary to activate MGP, they suggested that adequate dietary intake of vitamin K may be a necessary prerequisite in preventing the development of varicose veins.
"The increased calcification process in varicose veins could thus be due to incomplete MGP carboxylation as observed in other vascular diseases," wrote Cario-Toumaniantz. "As vitamin K is an essential cofactor for MGP carboxylation, it might be expected that the local vascular vitamin K status is insufficient in varicose vein to mediate full carboxylation of all newly formed MGP. "In varicose SMC cultures, our results showed that vitamin K supplementation inhibited the mineralization process, suggesting that in vitro, carboxylation of MGP could be partly induced and that the inhibitory effect of MGP could be restored," she added. The researchers called for future studies to analyse vitamin K levels in the walls of both varicose and healthy veins in order to deepen the understanding the MGP under-carboxylation mechanism.
Source: Journal of Vascular Research 2007, Volume 44, Pages 444-459, doi: 10.1159/000106189 "Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling"
Authors: C. Cario-Toumaniantz, C. Boularan, L.J. Schurgers, M.-F. Heymann, M. Le Cunff, J. Léger, G. Loirand, P. Pacaud