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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The early fine structural changes in the arteries of rats induced by excess vitamin D3 perorally or parenterally were essentially similar, except the latter had a more prominent toxic effect to the vascular wall. The ultrastructural features, incidental to calcification, included the appearance of increased ground substance with a separation of collagenous and elastic fibrils, and degenerative changes in smooth muscle cells. Atherosclerosis was greatly accelerated at the sites of vascular injury when cholesterol, cholic acid and thiouracil were added to the basal diet. Calcification was initially observed in relation to elastic fibrils or degenerated cells in the upper and middle layers of the arteries, although there were few such deposits in the thickened intima of the coronary arteries. Calcium deposition could not be a direct effect of hypercalcemia, but the functional activity of smooth muscle cells did seem to promote the mineralization of calcium and phosphate. Furthermore, vitamin D-induced sclerosis did not prevent intimal thickening of the arteries when vitamin D3 was withdrawn.
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PMID:Vitamin D sclerosis in rats. 22 74

The purpose of this study was to test the effectiveness of various doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) in an experimental rabbit model of athero-arteriosclerosis designed by Hass et al. (Amer. J. Pathol., 49 (1966) 739). This model, which involves the feeding of a hypercholesterolemic diet in conjunction with the administration of moderately high doses of vitamin D and nicotine, results in an extensive arterial disease with complicated lesions. EHDP was administered daily by subcutaneous injection at levels of 0.25, 1.0 and 2.5 mg/kg body weight beginning with the initiation of the atherogenic regimen. Results of chemical and histopathological analyses after 8 and 12 weeks of treatment indicate the following: (1) There was a dose-related inhibition of arterial calcification at 8 weeks. At 12 weeks, only the 2.5 mg/kg dose of EHDP resulted in reduced calcification. (2) EHDP administration appeared to influence arterial lipid-containing plaque formation in medium sized arteries at 12 weeks. There was no apparent effect of EHDP administration on serum cholesterol and triglyceride levels. (3) EHDP, at a dose of 2.5 mg/kg/day, inhibited the vitamin D induced hypercalcemia. (4) EHDP administration at 2.5 mg/kg/day almost totally inhibited the thromboarteritis accompanying this disease. (5) The data thus indicate that if arterial calcification is inhibited, the other morphological effects of this treatment regime are also inhibited. This effect occurred even though serum lipid levels were unaffected. The data therefore emphasize the role of calcification in the pathogenesis of this type of experimental atherosclerosis and perhaps in human disease as well.
Atherosclerosis
PMID:The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis. 81 8

We investigated the effect of 22-oxa-1,25-dihydroxyvitamin D3, a synthetic analogue of vitamin D3, on the production of prostacyclin by vascular tissues using rat aortic rings and A7r5 cells derived from fetal rat aortic smooth muscle. Prostacyclin synthesis by aortic rings of rats treated with 22-oxa-1,25-dihydroxyvitamin D3 was much higher than that of non-treated controls, but did not cause any significant hypercalcemia. Treatment with 22-oxa-1,25-dihydroxyvitamin D3 significantly increased the production of prostacyclin by A7r5 cells for 48 hours in a dose-dependent manner. In time-course studies, cells incubated with 22-oxa-1,25-dihydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 produced prostacyclin progressively over a period of 48 hours. The shortest period of incubation that produced a significant amount of prostacyclin compared with control cultures was 24 hours. We observed that treatment with 22-oxa-1,25-dihydroxyvitamin D3 induced cyclooxygenase mRNA in A7r5 cells. Our data suggest that 22-oxa-1,25-dihydroxyvitamin D3 may possibly be a protective substance against the development of atherosclerosis by modulating prostaglandin metabolism.
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PMID:A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxy-vitamin D3, stimulates the production of prostacyclin by vascular tissues. 151 73

A long-term hemodialysis patient with a giant intracranial vascular channel, which has been called a giant serpentine aneurysm, is presented. A 50-year-old man with an eight-year history of hemodialysis treatment was admitted because of headache, nausea and double vision. Computed tomographic scans and nuclear magnetic resonance revealed intracranial abnormal shadow. The left vertebral arteriography showed that the distal portion of the left vertebral artery was dilated to 17 mm in diameter. The basilar artery showed a large tortuous vascular channel and globular aneurysms over 25 mm in diameter. This giant serpentine aneurysm is a rather rare disease. To our knowledge, it has not been reported as a complication in a hemodialysis patient, although fourteen cases have been reported in the literature. In our case, several conditions such as long-term hypertension, hyperlipidemia, hypercalcemia, atherosclerosis and abnormal blood flow due to arteriovenous fistula for hemodialysis treatment might be considered to play a role in the formation of the giant serpentine aneurysms.
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PMID:Giant serpentine aneurysm in a long-term hemodialysis patient. 318 May 24

Nilvadipine and other calcium antagonists were studied for their effect on 1-alpha-hydroxyvitamin D3 (1 - alpha (OH)D3)-induced aortic calcium deposition in rats. The animals were treated orally with 1-alpha (OH)D3 (10 micrograms/kg) for 2 weeks. Calcium antagonists were given orally twice a day during the same period. The aortic calcium content in 1-alpha (OH)D3-treated rats increased to about 100 times that in the control. Nilvadipine reduced the aortic calcium deposition dose-dependently, with percent inhibition of 6, 43, 72 and 92%, at doses of 0.1, 1, 10 and 100 mg/kg, respectively. Similar activities were obtained for the other calcium antagonists except diltiazem which had no effect even at the largest dose of 100 mg/kg. According to the ED50 values, nilvadipine (2.2 mg/kg) was more potent than nifedipine (23.2 mg/kg), nicardipine (12.4 mg/kg) and verapamil (32.0 mg/kg). Scanning and transmission electron microscopy showed clear-cut degenerative changes in the endothelial cells after 1-alpha (OH)D3 treatment. Nilvadipine exerted a protective effect against these degenerative changes but not against 1-alpha (OH)D3-induced hypercalcemia. Furthermore, the drug had only minimal effect on in vitro calcification of the aorta. Our findings suggest that nilvadipine inhibits aortic calcification by protecting the aortic wall cells.
Atherosclerosis 1988 Oct
PMID:Protective action of a calcium antagonist, nilvadipine, against aortic calcium deposition--a pathogenic factor in atherosclerosis. 326 72

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.
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PMID:Magnesium metabolism in health and disease. 328 51

Certain clinical and morphologic cardiac observations are described in 18 necropsy patients, aged 33 to 58 years (mean 45 years) (14 women), with chronic hypercalcemia (11.6 to 34.4 mg/dl [19.4]) from one to nine years (mean five years). Primary hyperparathyroidism was present in nine patients and secondary hyperparathyroidism in the other nine (of renal origin in seven). Cardiac valve anular and coronary arterial calcific deposits were present in 10 patients (Group I) including four (mean age 51 years) with considerable narrowing of two or three of the four major epicardial coronary arteries. None of the other eight patients (Group II) had cardiac valve anular or cuspal calcific deposits; only two had coronary calcific deposits, small in each, and none had significant coronary luminal narrowing. Calcium was in the media ("medial calcinosis"), with or without intimal deposition, of the coronary arteries in five patients. Comparison of the patients in Group I to those in Group II disclosed similar mean ages, durations of hypercalcemia and serum calcium levels, but significantly (p less than 0.05) higher mean total serum cholesterol levels (216 versus 163 mg/dl) and heart weights (426 versus 320 g). This study demonstrates that chronic hypercalcemia is associated with accelerated deposition of calcium in the cardiac anuli and valvular cusps, in the media and intima of the coronary arteries and in individual myocardial fibers (dystrophic calcification), and that coronary intimal calcification may be associated with or produce luminal narrowing, especially in patients with serum total cholesterol levels over 200 mg/dl. Thus, chronic hypercalcemia may be viewed as a "risk factor" to accelerated coronary atherosclerosis.
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PMID:Effect of chronic hypercalcemia on the heart. An analysis of 18 necropsy patients. 728 28

Calcification and ossification of soft tissues occurs as a response to a variety of injuries such as atherosclerosis, myositis ossificans, and caseous necrosis. These injuries and others have as a unifying characteristic persistent necrotic tissue elements. Normal tissues may calcify under conditions of hypercalcemia or hyperphosphatemia. The initial mobilization of Ca and P following injury is rapid, as observed in calcergy. The mitochondria of cells, normally a storehouse of Ca, become preferential sites of precipitated Ca when cells are irreversibly injured, and act as foci of progressive calcification. Collagen fibers undergo calcification directly, principally when they are located within devitalized sites such as prosthetic heart valves, and direct calcification of collagen may predominate generally in dystrophic calcification. VArious porous sponges act as foci for calcification and ossification, and the utilization of porous implants may provide for the development of therapeutically useful calcifying and ossifying biomaterials.
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PMID:Mineralization of connective tissue surrounding implanted devices. 733 Nov 58

To determine whether metastatic calcification during neointima formation can result in neointimal calcification that simulates advanced human atherosclerosis, 32 giant Flemish rabbits (weight 5.5 +/- 0.6 kg) underwent overstretch balloon injury of bilateral iliac arteries and received diet therapy for 8 weeks: high cholesterol (2%) and low calcium-vitamin D2 regimen (250 mg of calcium carbonate orally 5 times weekly and 50,000 U of calciferol intramuscularly 3 times weekly; group 1; n = 5); low cholesterol (0.5%) and high calcium-vitamin D2 regimen (500 mg of calcium carbonate orally 5 times weekly and 100,000 U of calciferol intramuscularly three times weekly; group 2; n = 19); or 0% cholesterol and high calcium-vitamin D2 regimen (group 3; n = 8). The incidence of vascular calcification was highest (71.4%) in group 2. Eighty-one percent of calcification was medial. Residual strain measurements of 7 thoracic aortas from group 2 compared to normal thoracic aortas from 8 control rabbits showed that residual strain was significantly increased in the calcified atherosclerotic aortas (12.3% vs 5.2%; p = 0.001). We conclude that diet-induced hypercalcemia predominantly affects the media despite the presence of concomitant neointima formation from balloon artery injury with or without hypercholesterolemia and increases the residual strain more than twofold compared to normal thoracic aortas.
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PMID:Vascular effects of diet-induced hypercalcemia after balloon artery injury in giant Flemish rabbits. 757 83

The effects of clodronate, a bisphosphonate for the treatment of hypercalcemia, on the progress of atherosclerosis were studied in rabbits fed with a high-cholesterol (1%) diet and treated simultaneously with disodium clodronate 0 (saline), 1, 5, or 25 mg/kg intravenously twice a week for 6, 9, and 12 weeks. In 9 to 12 weeks, plasma total cholesterol increased from 0.8 +/- 0.3 mmol/L (mean +/- SD) in rabbits fed the standard diet to 46 +/- 17 mmol/L in animals subjected to high-cholesterol diet. Clodronate did not influence the cholesterol concentration in plasma. None of the parameters studied were changed by clodronate within 6 weeks after beginning the treatment. In 9 to 12 weeks (n = 7 to 9), plasma total Ca++ concentration was decreased from 3.55 +/- 0.12 mmol/L in the saline group to 3.36 +/- 0.16 mmol/L in the group on the greatest clodronate dose (p < 0.05). Free and esterified cholesterol and total Ca++ concentrations in the wall of thoracic aorta were reduced by the greatest dose of clodronate, compared with the groups treated with saline solution or smaller doses of the drug (p < 0.05). At 12 weeks, the greatest dose of clodronate also reduced the visible and lipid-stained atheromatous areas in the thoracic and abdominal aorta, compared with those in the saline and the other clodronate dose groups (p < 0.05). The results suggest that a high dose of clodronate inhibits the development of diet-induced atherosclerosis in rabbits.
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PMID:Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. 819 83


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