cholecalciferol and Vascular-Diseases

Fibroblast growth factors (FGF) constitute a large family of proteins with pleiotropic effects on development, organogenesis, and metabolism. The FGF19 subclass includes growth factors circulating with the blood referred to as endocrine FGF. Representatives of the FGF19 subclass, including FGF19, FGF21, and FGF23, act via FGFR receptors. The proteins of FGF19 subfamily influence the enterohepatic circulation of bile, participate in glucose and lipid metabolism regulation, and maintenance of phosphorus and vitamin D3 homeostasis. FGF19 and FGF21 are activated under different physiological and pathological conditions.

Topics: Adipose Tissue; Animals; Bile Acids and Salts; Carbohydrate Metabolism; Cholecalciferol; Diabetes Mellitus; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Klotho Proteins; Lipid Metabolism; Obesity; Phosphorus; Receptor, Fibroblast Growth Factor, Type 1; Vascular Diseases

Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death in these patients, especially, in patients with end-stage renal disease(ESRD). The pathological features in ESRD patients are intimal atherosclerosis and medial calcific sclerosis. The important risk factors for CVD in ESRD patients are hypertension, dyslipidemia and CKD bone and mineral disorder (CKD-MBD). Atherosclerosis has been evaluated by measurements of intima-media thickness and pulse-wave velocity. Although the target blood pressure still undetermined, hypertension would be treated with renin-angiotensin system inhibitors. In addition, treatment of dyslipidemia with statins may lead to favorable CVD outcome. Finally, inhibition of vascular calcification should be important by treatment with active vitamin D and sevelamer.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Bone Diseases, Metabolic; Calcinosis; Cholecalciferol; Chronic Disease; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Kidney Failure, Chronic; Polyamines; Risk Factors; Sevelamer; Tunica Intima; Vascular Diseases

The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency.. SLE patients with 25(OH) vitamin D (25(OH)D) levels <20 ng/mL were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to ≥32 ng/mL. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation.. Half of those who achieved 25(OH)D levels of ≥32 ng/mL experienced increases in FMD, whereas none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D-deficient SLE patients will require 35 patients in each group.. These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive, multi-arm, treat-to-target, serum-level trial design may increase the efficiency and likelihood of success of such a study.

Topics: Administration, Oral; Adult; Cholecalciferol; Dietary Supplements; Endothelium; Female; Humans; Inflammation; Lupus Erythematosus, Systemic; Male; Middle Aged; Pilot Projects; Vascular Diseases; Vitamin D Deficiency

Vitamin D or calcium supplementation may have effects on vascular disease and cancer.. Our objective was to investigate whether vitamin D or calcium supplementation affects mortality, vascular disease, and cancer in older people.. The study included long-term follow-up of participants in a two by two factorial, randomized controlled trial from 21 orthopedic centers in the United Kingdom.. Participants were 5292 people (85% women) aged at least 70 yr with previous low-trauma fracture.. Participants were randomly allocated to daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention.. All-cause mortality, vascular disease mortality, cancer mortality, and cancer incidence were evaluated.. In intention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR = 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) did not differ significantly between participants allocated vitamin D and those not. All-cause mortality (HR = 1.03; 95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI = 0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), and cancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differ significantly between participants allocated calcium and those not. In a post hoc statistical analysis adjusting for compliance, thus with fewer participants, trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated, although all results remain nonsignificant.. Daily vitamin D or calcium supplementation did not affect mortality, vascular disease, cancer mortality, or cancer incidence.

Topics: Aged; Aged, 80 and over; Calcium; Cause of Death; Cholecalciferol; Dietary Supplements; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Mortality; Neoplasms; Osteoporotic Fractures; Placebos; Time Factors; Vascular Diseases

Vascular calcification is prevalent in patients with chronic kidney disease and leads to increased cardiovascular morbidity and mortality. Although several reports have implicated mitochondrial dysfunction in cardiovascular disease and chronic kidney disease, little is known about the potential role of mitochondrial dysfunction in the process of vascular calcification. This study investigated the effect of α-lipoic acid (ALA), a naturally occurring antioxidant that improves mitochondrial function, on vascular calcification in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial membrane potential and ATP production, the disruption of mitochondrial structural integrity and concurrently increased production of reactive oxygen species. These Pi-induced functional and structural mitochondrial defects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol, subsequent activation of caspase-9 and -3, and chromosomal DNA fragmentation. Intriguingly, ALA blocked the Pi-induced VSMC apoptosis and calcification by recovery of mitochondrial function and intracellular redox status. Moreover, ALA inhibited Pi-induced down-regulation of cell survival signals through the binding of growth arrest-specific gene 6 (Gas6) to its cognate receptor Axl and subsequent Akt activation, resulting in increased survival and decreased apoptosis. Finally, ALA significantly ameliorated vitamin D(3) -induced aortic calcification and mitochondrial damage in mice. Collectively, the findings suggest ALA attenuates vascular calcification by inhibiting VSMC apoptosis through two distinct mechanisms; preservation of mitochondrial function via its antioxidant potential and restoration of the Gas6/Axl/Akt survival pathway.

Topics: Animals; Apoptosis; Axl Receptor Tyrosine Kinase; Calcium; Caspase 3; Caspase 9; Cells, Cultured; Cholecalciferol; Cytochromes c; DNA Fragmentation; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria; Muscle, Smooth, Vascular; Phosphates; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Receptor Protein-Tyrosine Kinases; Thioctic Acid; Vascular Calcification; Vascular Diseases

Abnormalities of bone mineral metabolism in patients with stage-5 chronic kidney disease may contribute to the high incidence of cardiovascular disease. Noninvasive imaging methods may help predict the simultaneous presence of vasculopathy and bone disease. Accordingly, we measured pulse wave velocity and bone mineral density (BMD), and T-scores (number of SDs below the BMD of a younger reference group) of the spine by both dual energy x-ray absorptiometry and quantitative computed tomography (QCT) in 110 maintenance hemodialysis patients. Older age, white race, diabetes mellitus, lower diastolic blood pressure, and lower albumin levels were associated with lower QCT-assessed T-scores (each P<0.05). After age and multivariable adjustment, pulse wave velocity (PWV) increased as QCT BMD decreased (the prevalence of PWV >or=9 m/s was 32.4%, 61.8%, and 76.5% for participants in the highest to the lowest tertile of QCT-assessed BMD; P<0.001). In contrast, there was no relationship between spine dual energy x-ray absorptiometry-BMD and PWV. In unadjusted models, thoracic spine QCT-assessed T-scores correlated significantly, albeit weakly, with aorta calcification (r=0.22; P=0.01) but not with coronary calcification. The odds ratio of PWV >or=9 m/s for patients taking vitamin D(3) or its analogs was 0.51 (95% CI: 0.19 to 1.39). In conclusion, low spine BMD is associated with increased PWV in stage-5 chronic kidney disease, supporting the notion of a close interaction of vascular and bone disease in this patient group. QCT and not dual energy x-ray absorptiometry should be used to assess spine BMD in dialysis patients.

Topics: Absorptiometry, Photon; Adult; Aged; Blood Pressure; Bone Density; Calcinosis; Cholecalciferol; Female; Humans; Kidney Diseases; Lumbar Vertebrae; Male; Middle Aged; Pulsatile Flow; Regional Blood Flow; Renal Dialysis; Tomography, X-Ray Computed; Vascular Diseases

Topics: Aorta; Calcinosis; Calcium Phosphates; Cholecalciferol; Pharmacology; Phosphates; Polyphosphates; Rats; Research; Toxicology; Vascular Diseases