vitamin-d-2 and Atherosclerosis

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

Atherosclerosis (AS) is a chronic inflammatory disease that contributes to multiple cardiovascular diseases (CVDs), and foam cell formation plays important roles in the progression of AS. There is an urgent need to identify new molecular targets for treating AS, and thereby improve the quality of life and reduce the financial burden of individuals with CVD.. An in vitro model of AS was generated by treating THP-1 cells and human aortic vascular smooth muscle cells (HA-VSMCs) with oxidized low-density lipoproteins (ox-LDLs). HA-VSMC proliferation and foam cell formation were detected by the MTT assay and Oil Red O staining. C-X-C motif chemokine 12 (CXCL12) expression was suppressed by siRNA. An AS rat model was established by feeding rats a high-fat diet and vitamin D2 for 3 weeks. Histopathology examinations were conducted by Hematoxylin and Eosin (H&E) staining and the levels ionized calcium-binding adapter molecule 1 (IBA1) and α smooth muscle actin (α-SMA) expression were determined by ELISA assays and immunohistochemistry.. An in vitro model of AS was established with THP-1 cells. CXCL12 expression in the model THP-1 cells was significantly increased when compared with its expression in control cells. Suppression of CXCL12 expression reduced the progression of AS in the cell model. Moreover, CXCL12 promoted AS in the in vivo rat model.. Our results suggest that CXCL12 plays an important role in promoting the progression of AS. Furthermore, inhibition of CXCL12 might suppress the development of AS by inhibiting HA-VSMC proliferation and their transformation to foam cells.

Topics: Animals; Atherosclerosis; Cell Proliferation; Chemokine CXCL12; Coculture Techniques; Diet, High-Fat; Disease Models, Animal; Endothelial Cells; Ergocalciferols; Foam Cells; Humans; Lipoproteins, LDL; Male; Rats, Sprague-Dawley; Signal Transduction; THP-1 Cells; Up-Regulation

Cocoa polyphenols are thought to reduce the risk of cardiovascular diseases. Thus, cocoa-containing foods may have significant health benefits. Here, we studied the impact of chocolate liquor on vascular lesion development and plaque composition in a mouse model of atherosclerosis. Apolipoprotein E (apoE)-knockout mice were assigned to two groups and fed a Western diet that contained 250 g/kg of either chocolate liquor or a polyphenol-free isoenergetic control paste for 16 weeks. In addition to fat, protein, and fibers, the chocolate liquor contained 2 g/kg of polyphenols. Compared with the control group, mice fed the chocolate liquor had larger plaque areas in the descending aorta and aortic root, which were attributed to a higher mass of vascular smooth muscle cells (VSMCs) and collagen. Vascular lipid deposits and calcification areas did not differ between the two groups. The aortic tissue level of interleukin-6 (IL-6) mRNA was 5-fold higher in the mice fed chocolate liquor than in the control mice. Chocolate-fed mice exhibited an increased hepatic saturated to polyunsaturated fatty acid ratio than the controls. Although the chocolate liquor contained 14 µg/kg of vitamin D

Topics: Animals; Apolipoproteins E; Atherosclerosis; Chocolate; Diet, High-Fat; Ergocalciferols; Male; Mice, Knockout; Plaque, Atherosclerotic

Atherosclerosis (AS) is an inflammatory disease involved in vascular inflammatory injury. The inflammasome is an important part of inflammatory diseases and participates in the vascular inflammatory injury. Resveratrol (RSV) possesses anti-inflammatory activities, but its effects on inflammasomes during vascular injury remain unclear. This study focused on the effects and mechanisms of RSV on inflammasomes during vascular injury.. Male Sprague-Dawley rats were treated with a purified diet or cholesterol-enriched diet combined with vitamin D2 (VD; 1.8 million units/kg/days, Po) and saline or RSV (50 mg/kg/days, Po) daily for 5 weeks. The concentrations and enzyme activities of related indicators were measured by a spectrophotometer or ELISA kit. Their gene and protein expression levels were analyzed by reverse transcription-polymerase chain reaction and Western blot, respectively.. Upon administration with RSV, rats with combined hyper cholesterol and VD demonstrated the following changes: the vascular histopathological changes were relieved, and the level of the von Willebrand factor decreased. The level of serum IL-1β, a marker of inflammasome activation, significantly decreased. The mRNA and protein expression levels of the three components of inflammasomes, namely, NOD-like receptor pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, and caspase-1, were downregulated. The effects of RSV were closely related to hypolipidemia (decrease in the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol combined with the expression of the lectin-like ox-LDL receptor and increase in high-density lipoprotein cholesterol), antioxidation (decrease in MDA levels and increase in SOD and GPx activities), and anti-inflammation (downregulation of the expression of IL-1β, intracellular adhesion molecule-1, and monocyte chemotactic protein-1). The mechanisms for the downregulation of NF-κB p65 and p38 MAPK expression, as well as the upregulation of SIRT1 expression, were analyzed.. This study proved that RSV inhibited inflammasome activation to protect vascular injury in vivo. RSV exhibited therapeutic potential in the treatment of vascular injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Aorta, Thoracic; Atherosclerosis; Carrier Proteins; Caspase 1; Ergocalciferols; Hypercholesterolemia; Inflammasomes; Inflammation; Lipid Peroxidation; Lipids; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Vitamins

This study investigated the protective effect of vitamin D analog paricalcitol combined with angiotensin-converting enzyme inhibitor (enalapril) on aortic oxidative injury in atherosclerotic mice.. Female mice were treated for 16 weeks as follows: (1) ApoE deficient + vehicle, (2) ApoE deficient + paricalcitol (200 ng 3 times a week), (3) ApoE deficient + enalapril (30 mg/l in drinking water), (4) ApoE deficient + paricalcitol + enalapril, and (5) wild-type controls.. ApoE-deficient mice developed hypertension which was prevented by enalapril or enalapril + paricalcitol treatment but not by paricalcitol treatment. Histology showed atherosclerotic plaque in the aorta of ApoE-deficient mice which was prevented by paricalcitol, enalapril, and paricalcitol + enalapril treatments. Aortic malondialdehyde levels, NADPH oxidase subunit p22(phox), manganese-superoxide dismutase (Mn-SOD), inducible nitric oxide synthase, monocyte chemoattaractant protein-1, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 protein expressions increased, whereas glutathione levels, CuZn-SOD, and endothelial protein expressions decreased in ApoE-deficient mice compared to controls. Treatment with paricalcitol and enalapril alone or in combination protected the inflammatory and oxidative endothelial injury of the aorta in atherosclerotic mice.. Combination therapy affords greater protection against aortic inflammatory and oxidative injury in atherosclerosis than monotherapy.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Apolipoproteins E; Atherosclerosis; Blood Pressure; Chemokine CCL2; Cyclooxygenase 2; Enalapril; Endothelium; Ergocalciferols; Female; Glutathione; Malondialdehyde; Mice; Mice, Knockout; NADPH Oxidases; Nitric Oxide Synthase; Oxidative Stress; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Vitamins

Recent data have shown that aortic valve stenosis (AS) is an active and highly regulated process which shares similarities with atherosclerosis. However, AS cannot be considered as a purely atherosclerotic phenomenon, and a hypercholesterolemic rabbit model might not be fully representative of human AS pathophysiology.. Twenty-eight New Zealand White rabbits were assigned to three groups: group 1 (no dietary supplement for three months); group 2 (0.3% cholesterol-enriched-diet + 50,000 IU/day vitamin D2 for six months); and group 3 (1% cholesterol-enriched-diet + vitamin D2 for three months). The peak aortic gradient and permeability index (outflow tract/aortic velocity-time-integral) were assessed, as well as calcium staining within the aortic valve and ascending aorta.. AS hemodynamic severity was not different among the groups. The peak gradient was 4 +/- 2 mmHg at baseline, 4 +/- 2 mmHg at three months in controls, 4 +/- 1 mmHg at three months and 6 +/-3 mmHg at six months in group 2, and 4 +/- 1 mmHg at three months in group 3 (p = NS). The permeability index was 64 +/- 7 at baseline, 60 +/- 12 at three months in controls, 63 +/- 14 at three months and 58 +/- 12 at six months in group 2, and 60 +/- 5 at three months in group 3 (p = NS). The aortic valve of cholesterol-enriched-diet rabbits was thickened but not calcified, whereas the ascending aorta was both thickened and calcified.. When using a hypercholesterolemic rabbit model plus vitamin D2, no adverse hemodynamic effect or aortic valve calcification was observed, despite a high-level and prolonged cholesterol-regimen supplementation. These results raise questions with regard to the extrapolation of this animal model to humans.

Topics: Animals; Aorta; Aortic Valve Stenosis; Atherosclerosis; Blood Flow Velocity; Calcinosis; Capillary Permeability; Cholesterol, Dietary; Ergocalciferols; Male; Microscopy; Models, Animal; Rabbits; Vitamins

We have previously proved that oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, plays a pivotal role in the development of atherosclerotic calcification (AC). The present study was performed to investigate whether tanshinone II A (TS II A), an anti-oxidant which has been shown to inhibit in vitro oxidation of LDL, has the effects to inhibit AC in rat model and by which, if any, mechanisms.. Rat AC model was induced by excessive vitamin D(2) (VD) and high cholesterol diet (HCD), which was proven to be successful histopathologically and biochemically.. Administration of AC rats with TS II A (35, 70 mg/kg) dose-dependently attenuated the AC pathological changes, meanwhile reduced the vessel contents of lipid and calcium. However, TS II A had no effects on serum levels of lipids, calcium and 25-OH VD. Further studies revealed that TS II A decreased serum concentration of oxLDL, reduced the superoxide anion production and malondialdehyde (MDA) in vessel. In addition, TS II A increased vessel Cu/Zn SOD activity, upregulated vessel mRNA and protein expression of Cu/Zn SOD.. The results suggested that TS II A significantly attenuated the AC in rat model, which might be attributed to its inhibition of oxLDL production independent of the serum levels of lipids, calcium and 25-OH VD, and that increasing of Cu/Zn SOD activity as well as mRNA and protein expression by TS II A might protect LDL against oxidation induced by superoxide anion in vessel.

Topics: Abietanes; Animals; Antioxidants; Aorta, Thoracic; Atherosclerosis; Calcinosis; Calcium; Cholesterol; Cholesterol, Dietary; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Induction; Ergocalciferols; Lipoproteins, LDL; Male; Malondialdehyde; Oxidative Stress; Phenanthrenes; Rats; Rats, Sprague-Dawley; RNA, Messenger; Superoxide Dismutase; Superoxides; Time Factors

Calcium and cholesterol play major roles in the formation of atherosclerosis. Whether severe atherosclerosis induced by co-administration of a mixture containing vitamin D2 (vit D2) and cholesterol can result in gastric hemorrhagic damage is unknown. Gastric oxidative stress and hemorrhagic ulceration in rats with atherosclerosis induced by co-administration of vit D2 and cholesterol and the protective effect of lysozyme chloride on this ulcer model were investigated.. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vit D2 and cholesterol to induce atherosclerosis. Control rats received the same volume of corn oil only. After 24-h fasting followed by gastric surgery, the rat stomachs were irrigated for 3 h with simulated rat gastric juice or normal saline. Various gastric mucosal ulcerogenic factors (acid back-diffusion, lipid peroxides, histamine concentration, and hemorrhagic ulcers) and defensive substances (mucosal glutathione and mucus secretion) were determined.. Augmentation of serum calcium concentration, total cholesterol, and low-density lipoprotein was observed in atherosclerotic rats. Greater mucosal ulcerogenic parameters and lower defensive substances were achieved in these rats. High correlation between decreased mucosal glutathione and ulceration as well as between increased mucosal lipid peroxide levels and ulceration was also found in the atherosclerotic rats. Daily intragastric lysozyme chloride dose-dependently protected gastric mucosal hemorrhagic damage in the atherosclerotic rats.. Atherosclerosis induced by co-administration of vit D2 and cholesterol could produce gastric oxidative stress and hemorrhagic ulcer that was ameliorated by lysozyme chloride in rats.

Topics: Animals; Atherosclerosis; Cholesterol; Corn Oil; Ergocalciferols; Gastric Juice; Gastric Mucosa; Glutathione; Male; Muramidase; Oxidative Stress; Peptic Ulcer Hemorrhage; Rats; Rats, Wistar

Topics: Arteriosclerosis; Atherosclerosis; Blood; Cholestanes; Cholesterol; Ergocalciferols; Vitamin D; Vitamins

Topics: Arteriosclerosis; Atherosclerosis; Cholesterol; Ergocalciferols; Hormones; Parathyroid Glands; Parathyroid Hormone; Paratyphoid Fever; Vitamin D; Vitamins