vitamin-k-1 and Inflammation

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Both conditions are rising in incidence as well as prevalence, creating poor outcomes for patients and high healthcare costs. Recent data suggests CKD to be an independent risk factor for CVD. Accumulation of uremic toxins, chronic inflammation, and oxidative stress have been identified to act as CKD-specific alterations that increase cardiovascular risk. The association between CKD and cardiovascular mortality is markedly influenced through vascular alterations, in particular atherosclerosis and vascular calcification (VC). While numerous risk factors promote atherosclerosis by inducing endothelial dysfunction and its progress to vascular structural damage, CKD affects the medial layer of blood vessels primarily through VC. Ongoing research has identified VC to be a multifactorial, cell-mediated process in which numerous abnormalities like mineral dysregulation and especially hyperphosphatemia induce a phenotype switch of vascular smooth muscle cells to osteoblast-like cells. A combination of pro-calcifying stimuli and an impairment of inhibiting mechanisms like fetuin A and vitamin K-dependent proteins like matrix Gla protein and Gla-rich protein leads to mineralization of the extracellular matrix. In view of recent studies, intercellular communication pathways via extracellular vesicles and microRNAs represent key mechanisms in VC and thereby a promising field to a deeper understanding of the involved pathomechanisms. In this review, we provide an overview about pathophysiological mechanisms connecting CKD and CVD. Special emphasis is laid on vascular alterations and more recently discovered molecular pathways which present possible new therapeutic targets.

Topics: Animals; Atherosclerosis; Cardio-Renal Syndrome; Disease Models, Animal; Endothelium, Vascular; Extracellular Vesicles; Heart Disease Risk Factors; Humans; Incidence; Inflammation; Mice; MicroRNAs; Myocytes, Smooth Muscle; Rats; Renal Insufficiency, Chronic; Tunica Media; Vascular Calcification; Vitamin K 1; Vitamin K Deficiency

Recent studies have highlighted the importance of vitamin K2 (VK2) in human health. However, there have been no clinical studies investigating the role of VK2 in the prevention or treatment of Alzheimer's disease (AD), a debilitating disease for which currently there is no cure. In reviewing basic science research and clinical studies that have connected VK2 to factors involved in AD pathogenesis, we have found a growing body of evidence demonstrating that VK2 has the potential to slow the progression of AD and contribute to its prevention. In our review, we consider the antiapoptotic and antioxidant effects of VK2 and its impact on neuroinflammation, mitochondrial dysfunction, cognition, cardiovascular health, and comorbidities in AD. We also examine the link between dysbiosis and VK2 in the context of the microbiome's role in AD pathogenesis. Our review is the first to consider the physiological roles of VK2 in the context of AD, and, given the recent shift in AD research toward nonpharmacological interventions, our findings emphasize the timeliness and need for clinical studies involving VK2.

Topics: Alzheimer Disease; Antioxidants; Apoptosis; Cardiovascular System; Gastrointestinal Microbiome; Humans; Inflammation; Microbiota; Microglia; Neurodegenerative Diseases; Vitamin K 1; Vitamin K 2

Cardiovascular disease is the major cause of death in the Western world, but some recent studies indicate that vitamin K may play a role in atherosclerosis protection.. The aim of this study was to evaluate the effect of phylloquinone supplementation on blood lipids, inflammatory markers and fibrinolytic activity in postmenopausal women.. Thirty-one postmenopausal women completed this placebo-controlled, randomized crossover study and received 500 microg phylloquinone or placebo in addition to their habitual diet during two periods of 6 weeks' duration. Blood concentration of lipids, inflammatory markers and fibrinolytic parameters were measured after each period.. Inflammatory markers, fibrinolytic parameters, total cholesterol and LDL-C were unaffected by the supplementation, whereas a 15% increase was seen in triacylglycerols (P = 0.015) and a 5% decrease in HDL-C (P = 0.06).. Six weeks supplementation with a dose of phylloquinone similar to that obtainable from the diet induced a deterioration of the lipid profile with no improvement in any of the other risk markers analysed. Thus, these results do not support a cardioprotective effect of vitamin K as has been suggested by others.

Topics: Aged; Antifibrinolytic Agents; Biomarkers; Cardiovascular Diseases; Cross-Over Studies; Dietary Supplements; Female; Humans; Inflammation; Lipids; Middle Aged; Postmenopause; Vitamin K 1

Studies have shown associations between reduced vitamin K status and poor cognitive function. However, despite this apparent link, direct studies measuring cognitive function, vitamin K status and inflammation are lacking. In the current study, The ELDERMET cohort was investigated to identify associations between cognition, vitamin K status and inflammation. The primary aim of the ELDERMET study was to investigate the relationship between gut bacteria, diet, lifestyle and health in 500 older Irish adults. Significant differences in serum phylloquinone, dietary phylloquinone and inflammatory markers were found across varying levels of cognitive function, after controlling for sex, age, body mass index (BMI), triglycerides and blood pressure. In addition, significantly higher levels of dietary phylloquinone were found in those with better cognition compared to those with the poorest function. Higher levels of inflammatory were also associated with poor cognition. Furthermore, both dietary and serum phylloquinone were significant independent predictors of good cognitive function, after controlling for confounders. This study highlights the importance of dietary vitamin K as a potentially protective cognitive factor; it also provides evidence for the correlation between cognition and inflammation. Strategies should be devised by which elderly populations can access rich dietary sources of phylloquinone to maintain cognition.

Topics: Aged; Aged, 80 and over; Cognition; Cognitive Dysfunction; Cohort Studies; Diet; Female; Humans; Inflammation; Inflammation Mediators; Ireland; Male; Nutritional Status; Vitamin K 1

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature

1. Sodium warfarin, given by oral or by parenteral route, displays a pronounced anti-inflammatory effect in the formaldehyde and carrageenan induced rat paw edema. This effect becomes patent not only when the warfarin application precedes the local injection of the irritant substance (prophylactic effect), but also when it is given to animals with already developed inflammatory reactions (therapeutic effect). 2. The active doses of Na warfarin lie between 0.5 and 5.0 mg/kg. Smaller as well as higher doses show a reduced anti-inflammatory effect. 3. A marked anti-inflammatory effect can be noted already 90 min after drug injection at a still normal prothrombin level. 4. Vitamin K1 (phylloquinone), given by oral or parenteral route, in doses from 1.6 mg/kg upwards, shows a marked anti-inflammatory effect both in the prophylactic and the therapeutic rat paw test. Vitamin K3 is devoid of any anti-inflammatory activity. 5. The anti-inflammatory effect of both sodium warfarin and of vitamin K1 in rats, is not interfered with by previous adrenalectomy.

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Formaldehyde; Inflammation; Male; Prothrombin; Rats; Time Factors; Vitamin K 1; Warfarin

Topics: Acetylcholine; Aerosols; Albumins; Anaphylaxis; Animals; Anti-Inflammatory Agents; Bradykinin; Bronchial Spasm; Edema; Erythema; Exudates and Transudates; Female; Gossypium; Granuloma; Guinea Pigs; Histamine; History of Medicine; In Vitro Techniques; Inflammation; Irritants; Kaolin; Lung; Male; Prednisolone; Rats; Serotonin; Ultraviolet Rays; Vitamin K; Vitamin K 1