14 research outputs found
Скульптура Азербайджана в трудах русских искусствоведов (в 60-80-х годах прошлого столетия)
CONTEXT: The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities and is associated with increased risk of diabetes and cardiovascular diseases. Phylloquinone, menaquinones, and vitamin K status are associated with several components of MetS, but the association with MetS has hardly been studied to date. OBJECTIVE: This study aimed to examine whether the intake and/or status of vitamin K is associated with MetS and its components. DESIGN: This study comprised two cohorts, one of 402 women and one of 400 men (age 40-80 y). At followup 625 participants were still alive and willing to participate. Data were analyzed both cross sectionally and longitudinally with Poisson and linear regression adjusted for multiple confounders. Baseline phylloquinone/menaquinone intakes were measured with a validated food frequency questionnaire and vitamin K status with serum desphospho-uncarborxylated matrix-Gla protein level. RESULTS: At baseline 270 (34.5%) participants had MetS and 171 (35.7%) at followup. Cross sectionally, high menaquinones intakes were associated (P(trend) = .08) with a lower prevalence of MetS with a prevalence ratio (PR) of 0.74 (95% confidence interval [CI], 0.54-1.03) for the highest vs the lowest tertile. At followup, the highest tertiles of menaquinones intake (PR = 0.62; 95% CI, 0.40-0.95) and vitamin K status (PR = 0.57; 95% CI, 0.38-0.87) were associated (P(trend) = .01) with a lower occurrence of MetS. These associations were mainly driven by relations with lower triacylglycerol concentrations for menaquinones and lower waist circumference for vitamin K status. Phylloquinone intake was not associated with MetS prevalence. CONCLUSIONS: This study shows that a high intake of menaquinones and high vitamin K status are associated with a lower occurrence of MetS
Vitamin-K-Dependent Protection of the Renal Microvasculature: Histopathological Studies in Normal and Diseased Kidneys
Vitamin-K-dependent carboxylation of matrix Gla protein (MGP) protects the macrocirculation against calcification. We recently reported in a multiethnic population study that the estimated glomerular filtration rate, a microvascular trait, decreased and the risk of chronic kidney disease increased with higher circulating levels of inactive dephospho-uncarboxylated MGP, a marker of vitamin K deficiency. These findings highlighted the possibility that vitamin K might have a beneficial effect on the renal microcirculation. To substantiate these epidemiological findings, we undertook a pilot study, in which we stained renal tissue samples obtained by biopsy from 2 healthy kidney donors and 4 patients with nephropathy for carboxylated and uncarboxylated MGP and calcium deposits. Three patients had renal calcifications, which were consistently associated with carboxylated and uncarboxylated MGP. Normal renal tissue was devoid of microcalcifications and staining for carboxylated and uncarboxylated MGP. Pending confirmation in a larger study covering a wider range of renal pathologies, these histopathological findings suggest that MGP might inhibit calcification not only in large arteries, as was known before, but in renal tissue as well, thereby highlighting potentially new avenues for promoting renal health, for instance by vitamin K supplementation
Gas6 protein: its role in cardiovascular calcification
BACKGROUND: Cardiovascular calcifications can be prevented by vitamin K and are accelerated by vitamin K antagonists. These effects are believed to be mainly mediated by the vitamin K-dependent matrix Gla protein. Another vitamin K-dependent protein, Gas6, is also expressed in vascular smooth muscle cells (VSMC). In vitro Gas6 expression was shown to be regulated in VSMC calcification and apoptotic processes. METHODS: We investigated the role of Gas6 in vitro using VSMC cultures and in vivo in young and old Gas6-deficient (Gas6(-/-)) and wildtype (WT) mice. In addition, Gas6(-/-) and WT mice were challenged by (a) warfarin administration, (b) uninephrectomy (UniNX) plus high phosphate diet, or (c) UniNX plus high phosphate plus electrocautery of the residual kidney. RESULTS: In vitro VSMC from WT and Gas6(-/-) mice exposed to warfarin showed increased apoptosis and calcified similarly. In vivo, aortic, cardiac and renal calcium content in all groups was similar, except for a lower cardiac calcium content in Gas6(-/-) mice (group a). Von Kossa staining revealed small vascular calcifications in both WT and Gas6(-/-) mice (groups a-c). In aging, non-manipulated mice, no significant differences in vascular calcification were identified between Gas6(-/-) and WT mice. Gas6(-/-) mice exhibited no upregulation of matrix Gla protein in any group. Cardiac output was similar in all treatment groups. CONCLUSIONS: Taken together, in our study Gas6 fails to aggravate calcification against the previous assumption
Vitamin K Status and Mortality After Kidney Transplantation: A Cohort Study
Background: Vitamin K modulates calcification by activating calcification inhibitors such as matrix Gla protein (MGP). In kidney transplant recipients, vitamin K insufficiency is common, but implications for long-term outcomes are unclear. Study Design: Single-center observational study with a longitudinal design. Setting & Participants: 518 stable kidney transplant recipients; 56% men; mean age, 51 +/- 12 (SD) years; and a median of 6 (IQR, 3-12) years after kidney transplantation. Factor: Plasma desphosphorylated-uncarboxylated MGP (dp-ucMGP) levels, reflecting vitamin K status. Outcomes: All-cause mortality and transplant failure. Results: At inclusion, median dp-ucMGP level was 1,038 (IQR, 733-1,536) pmol/L, with 473 (91%) patients having vitamin K insufficiency (defined as dp-ucMGP > 500 pmol/L). During a median follow-up of 9.8 (IQR, 8.5-10.2) years, 152 (29%) patients died and 54 (10%) developed transplant failure. Patients in the highest quartile of dp-ucMGP were at considerably higher mortality risk compared with patients in the lowest quartile (HR, 3.10; 95% CI, 1.87-5.12; P for trend <0.001; P for quartile 1 [Q1] vs Q4 <0.001). After adjustment for potential confounders, including kidney function and exclusion of patients treated with a vitamin K antagonist, this association remained significant. Patients in the highest quartile also were at higher risk of developing transplant failure (HR, 2.61; 95% CI, 1.22-5.57; P for trend = 0.004; P for Q1 vs Q4 = 0.01), but this association was lost after adjustment for baseline kidney function (HR, 1.20; 95% CI, 0.52-2.75; P for trend = 0.6; P for Q1 vs Q4 = 0.7). Limitations: Although MGP exists as various species, only dp-ucMGP was measured. No data were available for vascular calcification as an intermediate end point. Conclusions: Vitamin K insufficiency, that is, a high circulating level of dp-ucMGP, is highly prevalent in stable kidney transplant recipients and is associated independently with increased risk of mortality. Future studies should address whether vitamin K supplementation may lead to improved outcomes after kidney transplantation. (C) 2015 by the National Kidney Foundation, Inc
The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease
Background: Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylatedMGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk. Methods: We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays. Results: Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP >= 977 pmol/L or t-ucMG
Vitamin K dependent protection of renal function in multi-ethnic population studies
Background: Following activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but
its role in preserving renal function remains unknown.
Methods: In 1166white Flemish (mean age, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), we correlated
estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD
[KDOQI stages 2â 3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear
and logistic regression.
Results: Among Flemish and white and black Africans, between-group differences in eGFR (90, 100 and
122 mL/min/1.73 m2), dp-ucMGP (3.7, 6.5 and 3.2 μg/L), and CKD prevalence (53.5, 28.7 and 10.5%)
were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P â ¥ 0.075).
For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P = 0.023), 1.0 (P = 0.56), 2.8 (P = 0.0012)
and 2.1 (P b 0.0001) mL/min/1.73 m2 in Flemish, white Africans, black Africans and all participants combined;
the odds ratios for moving up one CKD stage were 1.17 (P = 0.033), 1.03 (P = 0.87), 1.29 (P = 0.12) and 1.17
(P = 0.011), respectively.
Interpretation: In the general population, eGFR decreases and CKD risk increaseswith higher dp-ucMGP, a marker
of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health.
© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY licensepublisher: Elsevier
articletitle: Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies
journaltitle: EBioMedicine
articlelink: http://dx.doi.org/10.1016/j.ebiom.2016.01.011
content_type: article
copyright: Copyright © 2016 The Authors. Published by Elsevier B.V.status: publishe
Vitamin K Dependent Protection of Renal Function in Multi-ethnic Population Studies
Background: Following activation by vitamin K (VK), matrix Gla protein (MGP) inhibits arterial calcification, but its role in preserving renal function remains unknown.
Methods: In 1166 white Flemish (mean age, 38.2 years) and 714 South Africans (49.2% black; 40.6 years), we correlated estimated glomerular filtration (eGFR [CKD-EPI formula]) and stage of chronic kidney disease (CKD [KDOQI stages 2–3]) with inactive desphospho-uncarboxylated MGP (dp-ucMGP), using multivariable linear and logistic regression.
Results: Among Flemish and white and black Africans, between-group differences in eGFR (90, 100 and 122 mL/min/1.73 m2), dp-ucMGP (3.7, 6.5 and 3.2 μg/L), and CKD prevalence (53.5, 28.7 and 10.5%) were significant, but associations of eGFR with dp-ucMGP did not differ among ethnicities (P ≥ 0.075). For a doubling of dp-ucMGP, eGFR decreased by 1.5 (P = 0.023), 1.0 (P = 0.56), 2.8 (P = 0.0012) and 2.1 (P < 0.0001) mL/min/1.73 m2 in Flemish, white Africans, black Africans and all participants combined; the odds ratios for moving up one CKD stage were 1.17 (P = 0.033), 1.03 (P = 0.87), 1.29 (P = 0.12) and 1.17 (P = 0.011), respectively.
Interpretation: In the general population, eGFR decreases and CKD risk increases with higher dp-ucMGP, a marker of VK deficiency. These findings highlight the possibility that VK supplementation might promote renal health