vitamin-d-2 and Vascular-Diseases

The articles providing answers to the questions on vascular calcification of most interest from a clinical point of view were selected. 1. How is it measured?: Studies showing the clinical utility of different tools to quantify it were analyzed. 2. What does it measure?: Both in dialysis patients and the general population, vascular calcification and arterial stiffness are prognostic factors for morbidity and mortality. Other markers such as fetuin-A are associated with mortality in patients on hemodialysis but not in patients in early stages of chronic kidney disease. 3. What causes it?: In two selected studies, it was demonstrated again that low bone turnover and diabetes cause cardiovascular disease and vascular calcification, respectively. 4. How is it treated?: There is still no clinical evidence of regression of vascular calcification. However, a prospective study in new hemodialysis patients showed that sevelamer compared to calcium compounds slows the progression of vascular calcification and confers greater survival. A study comparing both compounds in chronic hemodialysis patients showed that sevelamer only had a benefit on survival in patients older than 65 years. It remains to be demonstrated whether the good experimental results of paricalcitol and cinacalcet are confirmed in prospective clinical studies.

Topics: Aged; Animals; Atherosclerosis; Calcinosis; Chronic Disease; Cinacalcet; Coronary Artery Disease; Diabetes Complications; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Diseases; Mice; Mice, Knockout; Multicenter Studies as Topic; Naphthalenes; Polyamines; Randomized Controlled Trials as Topic; Renal Artery; Sevelamer; Tomography, Spiral Computed; Tomography, X-Ray Computed; Vascular Diseases

Vitamin D sterols may modulate vascular response to inflammation and vascular calcification (VC).. Rat aortic rings (RARs) and human vascular smooth muscle cells (HVSMCs) were treated in vitro with phosphate (P), tumour necrosis factor alpha (TNF-α), calcitriol (CTR) and paricalcitol (PCT). Rats having undergone subtotal nephrectomy (Nx) (n = 66) on a high-phosphorus diet were treated with Escherichia coli lipopolysacharide (LPS) (40-400 μg/kg/day) or LPS plus CTR (80 ng/kg/48 h) or LPS plus PCT (240 ng/kg/48 h) for 14 days.. In vitro, the addition of TNF-α to the medium increased the mineral content of RAR and HVSMC. Treatment with both vitamin D analogues decreased bone morphogenetic protein 2 but did not modify Runx-2. Calcification was prevented only by PCT. In vivo, treatment with LPS increased plasma levels of TNF-α, monocyte chemotactic protein-1 and interleukin-1alfa and induced calcification. The concomitant administration of LPS with either CTR or PCT led to a significant decrease in cytokine plasma levels and the decrease was more accentuated after treatment with PCT than with CTR. Rats treated with CTR showed an elevation in aortic Ca and marked Von Kossa staining; however, rats treated with PCT did not increase aortic Ca and did not show Von Kossa staining.. Treatment with PCT resulted in more marked anti-inflammatory effect than treatment with CTR and, as opposed to CTR, PCT prevented VC.

Topics: Animals; Aorta; Blood Pressure; Blotting, Western; Bone Density Conservation Agents; Calcinosis; Calcitriol; Calcium; Cells, Cultured; Cytokines; Ergocalciferols; Female; Humans; Inflammation; Lipopolysaccharides; Muscle, Smooth, Vascular; Nephrectomy; Phosphorus; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Uremia; Vascular Diseases

We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio.. Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification.. We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease.. Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments.. We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings.

Topics: Animals; Aorta; Blood Pressure; Bone Density Conservation Agents; Calcinosis; Calcitriol; Calcium; Cells, Cultured; Ergocalciferols; Gene Expression; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nephrectomy; Osteoprotegerin; Parathyroid Hormone; Phosphorus; RANK Ligand; Rats; Rats, Sprague-Dawley; Vascular Diseases; Vitamin D

Calcium dobesilate (DOBE) is an orally administered angioprotective agent which is used in some vascular diseases such as diabetic retinopathy, although its mechanism of action is not yet fully understood. The aim of this work was to correlate previous rising single quote, left (low)in vitro' findings carried out in our laboratory with an rising single quote, left (low)ex vivo' model of endothelium-injury by overdose of vitamin D2. Male New Zealand White rabbits were used. The study was divided into two protocols. Protocol 1: 10 days of treatment; and Protocol 2: 30 days of treatment. Rabbits in each group were treated with vitamin D2 (200"000 IU day-1) for the first 2 days and two groups were subsequently treated with DOBE at different doses (50 mg kg-1 per day or 500 mg kg-1 per day). The concentration-response curve induced by NA (10(-8)-10(-4) M) in aorta arteries was shifted downwards in the groups treated with DOBE (in both Protocol 1 and 2), whereas only in Protocol 2 (30 days of treatment) was this curve affected in the hypervitaminic group. The endothelium-dependent relaxation induced by ACh (10(-8)-10(-5) M) decreased in the hypervitaminic groups (in both Protocol 1 and 2) but only in Protocol 2 (30 days of treatment) was the endothelium-dependent relaxation restored to normal (control, untreated group) in both DOBE-treated groups. The endothelium-independent relaxation induced by sodium nitroprusside (SNP) (10(-8)-10(-4) M) decreased in the hypervitaminic groups only in Protocol 1. We did not find differences in the DOBE-treated groups in any protocol compared with the control (untreated) group. These findings show evidence that DOBE restored endothelial functionality in endothelium-injured rabbit aorta only after 30 days of treatment. (c) 1998 The Italian Pharmacological Society.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Calcium Dobesilate; Endothelium, Vascular; Ergocalciferols; In Vitro Techniques; Male; Nitric Oxide Donors; Nitroprusside; Rabbits; Vascular Diseases; Vasodilation

An observational study was made of the localization of experimental calcification of blood vessels induced by hypervitaminosis D in 15 stock rabbits, in 10 rabbits with arteriovenous fistulae, and in 6 rabbits with experimental saccular aneurysms. An arteriotomy and a phlebotomy were performed on several animals from each group. The pulmonary trunk, aorta, common carotid arteries, and external jugular veins were dissected and stained with silver nitrate to demonstrate calcification macroscopically. The first major bifurcation from 37 renal arteries from these animals was examined by the serial section technique to localize calcification about the arterial forks histologically. There was evidence that early calcification was flow related with a predilection for sites where atrophic lesions occur. Proliferative lesions in which matrix vesicles are abundant exhibited no such predisposition. It was concluded that matrix vesicles do not appear to be susceptible to vitamin D calcification. The topography of the experimental calcification differed from that of diet-induced lipid deposition.

Topics: Animals; Aorta; Arteriovenous Shunt, Surgical; Calcinosis; Carotid Arteries; Ergocalciferols; Female; Hemodynamics; Intracranial Aneurysm; Jugular Veins; Male; Rabbits; Regional Blood Flow; Renal Artery; Vascular Diseases

Topics: Animals; Aorta; Aortic Diseases; Ergocalciferols; Female; Glycosaminoglycans; Hydroxyproline; Male; Minerals; Rabbits; Sex Factors; Vascular Diseases