vitamin-k-1 and Atherosclerosis

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

Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited.. We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design.. Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial.. The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01].. Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Topics: Aged; Atherosclerosis; Calcium; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Dietary Supplements; Disease Progression; Double-Blind Method; Ethnicity; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors; Vascular Calcification; Vitamin K 1

Background Dietary vitamin K (K

Topics: Atherosclerosis; Cardiovascular Diseases; Denmark; Diet; Female; Hospitalization; Humans; Incidence; Male; Middle Aged; Nutrition Surveys; Nutritive Value; Prospective Studies; Protective Factors; Recommended Dietary Allowances; Risk Assessment; Risk Factors; Time Factors; Vitamin K 1; Vitamin K 2

Vascular calcification is commonly observed in atherosclerosis and diabetes. The renin-angiotensin II system is associated with the regulation of arterial stiffening. The aim of this study was to examine whether the angiotensin-converting enzyme inhibitors captopril attenuates artery calcification.. The rat model of arterial calcification was established by a combination of warfarin and vitamin K1. Two weeks after the induction of arterial calcification, captopril treatment was initiated. One week after captopril treatment, aortic arteries were examined to determine the calcification morphology and the connexin 43 expression. Matrix Gla protein (MGP), receptor activator of nuclear factor-κB ligand (RANKL) and extracellular regulated protein kinase (ERK) pathways were examined.. The morphology of the calcified arteries was significantly attenuated after captopril treatment. Consistently, captopril inhibited the increased connexin 43 expression and enhanced the decreased MGP expression in calcification arteries. Furthermore, captopril enhanced the decreased SM22 expression in calcified arteries by fluorescence assay. Finally, the calcification arteries increased the p38, p-ERK and RANKL expression, which were downregulated by captopril treatment.. We concluded that captopril attenuated the increased connexin 43 expression and enhanced the MGP and SM22 expression levels, which are associated with the inactivation of p-ERK, p38 and RANKL pathways in rat aortic arteries.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Arteries; Atherosclerosis; Calcium-Binding Proteins; Captopril; Connexin 43; Down-Regulation; Extracellular Matrix Proteins; Extracellular Signal-Regulated MAP Kinases; Male; Matrix Gla Protein; Microfilament Proteins; Muscle Proteins; RANK Ligand; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Up-Regulation; Vascular Calcification; Vascular Stiffness; Vitamin K 1; Warfarin

Vitamin K is integral to haemostatic function, and in vitro and animal experiments suggest that vitamin K can suppress production of inflammatory cytokines. To test the hypothesis that higher vitamin K status is associated with lower haemostatic activation and inflammation in community-dwelling adults, we analysed the cross-sectional association between serum phylloquinone (vitamin K1) with haemostatic and inflammatory biomarkers in 662 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) [mean (SD) age=62 (10) years; 46% female; 37% Caucasian, 25% African-American, 25% Hispanic, 13% Chinese-American]. Following adjustment for demographic and lifestyle characteristics, medication use, triglycerides and body mass index, those in the highest quartile of serum phylloquinone had significantly lower circulating interleukin-6 [adjusted mean (SEM) pmol/l: quartile 4 (Q4)=1.22 (0.07), quartile 1 (Q1)=1.45 (0.07); p-trend<0.01], C-reactive protein [adjusted mean (SEM) mg/dl: Q4=1.57 (0.11), Q1=2.08 (0.18); p-trend=0.02], soluble intercellular adhesion molecule-1 [adjusted mean (SEM) ng/ml: Q4=247 (11), Q1=288 (11); p-trend=0.02], and plasmin-antiplasmin complex [adjusted mean (SEM) nmol/l: Q4=4.02 (0.1), Q1=4.31 (0.1), p-trend=0.04]. We detected an interaction between age and serum phylloquinone with respect to factor VIII and D-dimer (interaction p-values=0.03 and 0.09, respectively). Among participants ≥70 years, serum phylloquinone was inversely associated with factor VIII activity (p-trend=0.06) and positively associated with D-dimer (p-trend=0.01), but was not associated with either marker among participants <70 years (both p≥0.38). In contrast, dietary phylloquinone intake was not associated with any inflammatory or haemostatic biomarker evaluated (all p-trend>0.11). These findings are consistent with laboratory-based studies that suggest a possible anti-inflammatory role for vitamin K. Whether or not these associations predict clinical outcomes linked to elevated inflammation or haemostatic activation remains to be determined.

Topics: Adult; Age Factors; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Ethnicity; Female; Hemostasis; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Middle Aged; Residence Characteristics; United States; Vitamin K 1