vitamin-k-1 and Aortic-Diseases

To investigate the association of plasma phylloquinone concentrations with coronary artery calcification (CAC) and vascular calcification.. In a prospective cohort of 508 postmenopausal women, plasma phylloquinone concentrations were measured by high-pressure liquid chromatography. Calcification was measured in the coronary arteries, aortic valve, mitral valve, and thoracic aorta by multidetector computed tomography. To combine these calcification scores, we dichotomized each of the 4 areas into present or absent. Because of the continuous measurement of CAC, we categorized this as calcification present if Agatston score was >0, and calcification score was calculated as the sum of the calcified areas. Multivariate-adjusted prevalence ratios and odds ratios were estimated using Poisson regression and multinomial logistic regression. After 8.5 years of follow-up, 22% of the women had no calcification, whereas 5% had calcification in all measured areas. Detectable phylloquinone concentrations were associated with increased CAC compared with nondetectable phylloquinone concentrations with a prevalence ratio of 1.34 (95% confidence interval, 1.01-1.77). When dividing women with detectable phylloquinone concentrations into low detectable (>0-0.70 nmol/L) and moderate to high detectable (>0.70 nmol/L) phylloquinone concentrations versus nondetectable phylloquinone concentrations, both were associated with increased CAC with a prevalence ratio of 1.32 (95% confidence interval, 0.99-1.76) and 1.36 (95% confidence interval, 1.02-1.81), respectively. Detectable phylloquinone concentrations were not associated with the number of calcified areas with an odds ratio(no versus ≥ 3 areas calcifications) of 1.60 (95% confidence interval, 0.65-3.99; P=0.31).. Detectable phylloquinone concentrations are not associated with reduced vascular calcification but seemed to be associated with an increased prevalence of CAC.

Topics: Aged; Aortic Diseases; Aortography; Biomarkers; Chromatography, High Pressure Liquid; Coronary Angiography; Coronary Artery Disease; Female; Healthy Volunteers; Humans; Logistic Models; Middle Aged; Multidetector Computed Tomography; Multivariate Analysis; Netherlands; Odds Ratio; Postmenopause; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Vascular Calcification; Vitamin K 1

We sought to determine whether carbonic anhydrase (CA), which plays an important role in bone resorption, contributes to vascular mineral loss induced by an endothelin receptor antagonist.. Wistar rats were compared with rats receiving warfarin and vitamin K1 (WVK) for 8 weeks alone or in association with the endothelin receptor antagonist darusentan (30 mg/kg per day), the CA inhibitor acetazolamide (100 mg/kg per day), or both for the last 4 weeks. Rats were also treated with WVK for 5 or 6 weeks, and darusentan was added for the last week or last 2 weeks of treatment, respectively. Treatment with WVK produced medial elastocalcinosis in the aorta and carotid arteries. Immunohistochemistry revealed that CA II was already abundant in the adventitia and in calcified areas of aortic sections from WVK-treated rats. Darusentan did not significantly modify its abundance or distribution. In contrast, CA IV immunostaining, which was weak in WVK-treated rats, became apparent after 1 week of darusentan treatment and declined toward basal levels thereafter. These findings were confirmed by a parallel increase in CA IV protein abundance and activity in the aorta. The mineral loss induced by darusentan was blunted by acetazolamide treatment, confirming the functional relevance of the biochemical findings. Moreover, CA IV immunostaining was enhanced much later in the carotids, where darusentan did not cause regression of elastocalcinosis.. Vascular mineral loss induced by the blockade of endothelin receptors seems dependent on the activation of membrane-bound CA IV, suggesting that mineral loss may proceed via local changes in pH similar to that seen in bone resorption.

Topics: Animals; Aorta; Aortic Diseases; Calcinosis; Calcium; Carbonic Anhydrase II; Carbonic Anhydrase IV; Carotid Arteries; Endothelin Receptor Antagonists; Enzyme Activation; Hemodynamics; Male; Phenylpropionates; Pyrimidines; Rats; Rats, Wistar; Remission Induction; Vitamin K 1; Warfarin

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Topics: Aortic Diseases; Arteriosclerosis; Calcinosis; Cholesterol; Cholesterol, HDL; Coronary Disease; Diet; Energy Intake; Female; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Netherlands; Odds Ratio; Prospective Studies; Risk Factors; Sex Characteristics; Vitamin K 1; Vitamin K 2

We have previously shown that an endothelin receptor antagonist can regress medial arterial calcification in a rat model. The aim of this study was to characterize the phenotypic changes of vascular smooth muscle cells during calcification and mineral loss, in order to understand better the underlying mechanisms. Control Wistar rats were compared with rats treated only with warfarin/ vitamin K1 (15 mg/kg per day) for 8 weeks, or in combination with darusentan (30 mg/kg per day) for the final 4 weeks. Vascular smooth muscle cell, bone cell and macrophage phenotypes were evaluated by the local expression of alpha-actin, tartrate-resistant acid phosphatase and ED-1, respectively. Proteins involved in the modulation of bone resorption like osteopontin and osteoprotegerin were also evaluated by immunohistochemistry. The warfarin/vitamin K1 treatment increased medial arterial calcification ninefold (P < 0.05). At sites of calcification, there was a decrease in alpha-actin localization, and an appearance of osteopontin immunostaining. Histochemical and immunostaining for osteoclast and macrophage markers, as well as for osteoprotegerin, were negative. Although the extent of calcification foci was reduced by darusentan, protein localization in the calcified areas was not modified. Thus, the development of medial arterial calcification produces a phenotypic change in vascular smooth muscle cells that does not appear to be normalized in regions remaining calcified during mineral loss.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Macrophages; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteoclasts; Osteopontin; Osteoprotegerin; Phenotype; Phenylpropionates; Pyrimidines; Rats; Rats, Wistar; Receptors, Endothelin; Vitamin K 1; Warfarin