Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malondialdehyde (MDA)-modified low density lipoprotein (LDL) can stimulate the accumulation of cholesteryl esters in cultured macrophages through its interaction with specific scavenger receptors. It has been speculated that such interaction occurs in vivo thus contributing to the formation of foam cells within atherosclerotic lesions. This report describes the development of new tools in the form of a specific assay for MDA-LDL to investigate this hypothesis. We have immunized BALB/c mice with malondialdehyde mouse low density lipoproteins and antibodies against malondialdehyde human low density lipoproteins were generated. Monoclonal antibodies were produced using hybridoma techniques and one particular clone (EB 7-3) was expanded for further studies. The immunoreactivity of several antigens was tested using antibody EB 7-3 in an enzyme-linked immunosorbent assay (ELISA). In a typical assay malondialdehyde human LDL (with at least 40% of lysines modified) was coated (2 micrograms/ml, 100 microliter) in 96-well microtiter plates. Antibody plus one of several antigens were then added and the interaction between the antibody and coated antigen was measured using alkaline phosphatase-conjugated affinity purified goat anti-mouse immunoglobulin. The binding of antibody EB 7-3 to wells coated with malondialdehyde-LDL was competitively inhibited by malondialdehyde-LDL added in solution, with half maximal inhibition occurring at 150 +/- 80 ng/ml. In addition, the ability of malondialdehyde-LDL to inhibit this interaction was proportional to the degree of modification: the more lysines were modified the more did malondialdehyde-LDL inhibit the binding of antibody EB 7-3 to coated malondialdehyde-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1987 Jun
PMID:Immunogenicity of malondialdehyde-modified low density lipoproteins. Studies with monoclonal antibodies. 244 16

Twelve male M. fascicularis monkeys were divided into two groups of 6 animals each. One group (BASAL) was fed a diet containing 24% protein, 38% carbohydrate and 20% fat, while the other group (ATHER) received an identical diet with the addition of 4.08 g/kg diet cholesterol. The animals were studied over a 4-year period. Blood samples were regularly collected, ECGs taken and carotid artery status evaluated by duplex ultrasound scanning. Lipid xanthomas were monitored by visual inspection. The ATHER group experienced a rapid and sustained rise in serum total cholesterol, concomitant with depression of HDL-cholesterol. In general, triglycerides were significantly higher in ATHER animals. Routine clinical analysis revealed lower hematocrit and hemoglobin, and elevated BUN and alkaline phosphatase in the treated group. Lipid xanthomas were detected early in the ATHER animals, progressing until infiltration was evident on the entire body surface. There were no differences in ECGs between the groups. At approximately 17 months posttreatment, stenosis was apparent in the carotid arteries of treated animals, rising to an average of 90% at study termination. These results indicate that diet-induced carotid atherosclerosis can be monitored non-invasively in the primate with minimum risk to the animal.
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PMID:Clinical profile of a 4-year primate atherosclerosis model. 268 88

Hyperlipoproteinaemia may represent a high risk factor in the pathogenesis of atherosclerosis, especially for the coronary heart disease. This metabolic disorder should therefore be treated. Strict diet is the basis of the treatment. In case the lipoprotein level does not normalize by means of diet, medicamentous therapy ought to be applied in addition. A total of 269 individuals suffering from hyperlipoproteinaemia have been treated in this study. According to Fredrickson there were 35 with Type IIa, 134 with Type IIb, 32 with Type IV and 68 with Type V. All of them had been previously treated with diet for at least three months. Afterwards, they were treated with fenofibrate (Katalip) in a dosage of 100 mg, 2 capsules in the morning and 1 in the evening. Biochemical parameters were checked a month after start of therapy. Cholesterol (-20%, -17%, -114%, -224%), triglycerides (-31%, -37%, -47%, -704), LDL cholesterol (-23%, -19%, -11% no significant, -31%), VLDL cholesterol (-25%, -29%, -32%, -59%), atherosclerosis index (-27%, -28%, -28%, -55%), urea (-5% no significant, -21%, -22%, -28%), gamma GT (-23%, -25%, -15% no significant, -39%) of patients with Type IIa, IIb, IV and V have decreased significantly (P less than 0.05), whereas the value of HDL cholesterol increased (0% no significant, +20%, +12%, +29%). No statistically significant changes during the therapy were observed in alkaline phosphatase (-8%, -9%, -11%, -10%), SGOT (-3%, -8%, +5%, -15%), SGPT (-22%, +4%, -18%, -15%) and glucose (-17% significant, -5%, -7%, -10%). Fenofibrate decreases the risk of the development of atherosclerosis by lowering lipoproteins and uric acid level.
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PMID:[The effect of fenofibrate in various types of hyperlipoproteinemias]. 274 11

Early atherosclerotic lesions in human aortas less than five hours postmortem were studied by light microscopy (20 cases) and electron microscopy (10 cases), to determine the morphological and cytochemical character of calcium deposition in the lesions. Routine and multiple special stains by light microscopy demonstrated atherosclerotic (intimal) calcium to be deposited as fine grains, ring-shaped droplets or small needle-shaped crystals, and medial calcium as fine grains or ring-shaped droplets. The calcium deposits were frequently associated with the PAS-positive basal lamina surrounding smooth muscle cells. In the intimal lesions the calcium deposits were often associated with fine granular lipid, while this association was much less frequent in the media. Calcium in atherosclerotic intima was generally not closely associated with elastic fibers but in the media was often deposited along or near elastic fibers. By electron microscopy the atherosclerotic lesions were composed of many smooth muscle cells (with or without lipid droplets), newly formed elastic fibers, amorphous ground substance, a few collagen fibrils and many membrane-limited matrix vesicle-like structures, 100-700 nm diameter. Many similar vesicles were present between the elastic laminae of the media. With the potassium pyroantimonate technique for demonstrating calcium, reaction products were most concentrated within these matrix vesicles but were also present in mitochondria of smooth muscle cells, within extracellular mitochondria-like structures, in pericellular basal lamina-like material and loosely dispersed in the interstitial ground substance. All elastic fibers were negative for calcium by this technique. The membrane of the matrix vesicle-like structures were cytochemically positive for alkaline phosphatase and adenosine triphosphatase. These studies suggest that calcification in human atherosclerosis and media is related to smooth muscle cell degeneration and that the major initial loci for calcium deposition are matrix vesicles from degraded cells, comparable to osteogenic calcification of cartilage.
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PMID:Calcification in atherosclerosis. I. Human studies. 294 18

Growing rats were fed ad libitum soy protein isolate (SPI) or its peptic (SPI-P) or tryptic digest (SPI-T) for a month and their sera were examined for cholesterol and triglyceride levels and enzyme activities such as cholinesterase, glutamate-pyruvate transaminase (GPT) and alkaline phosphatase. The rats fed SPI-P or SPI-T were inferior in growth to those fed SPI. Similarly, the serum glyceride level was lower in the SPI-P and SPI-T groups than in the SPI group. On the other hand, a significant difference was found in the serum cholesterol level between the SPI-P and SPI or SPI-T groups but not between the SPI and SPI-T groups. A similar tendency was observed for serum GPT and alkaline phosphatase activities, although there were no significant differences among dietary groups in small intestinal enzyme activities. As for the atherogenic index being a risk factor inducing atherosclerosis, the order of its value was SPI-P less than SPI less than SPI-T.
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PMID:Effect of feeding peptic digest of soy protein isolate on rat serum cholesterol. 310 Jul 38

Lipid, carbohydrate and protein metabolic parameters, such as triglycerides, total and alpha-cholesterol, total protein and albumin, urea nitrogen, creatinine, glucose and the activity of alanine and aspartate aminotransferases, alkaline phosphatase, total lactate dehydrogenase and creatine phosphokinase, were measured in 50 patients with obliterating atherosclerosis and 60 patients with arteritis. The latter showed more marked lipid metabolic disturbance, as compared to the former, as well as indirect signs of hepatic dysfunction.
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PMID:[Characteristics of metabolism in patients with arteriosclerosis obliterans and arteritis]. 323 41

In order to clarify whether hemodialysis treatment accelerates atherosclerosis, forty-two patients undergoing chronic hemodialysis were investigated. Because it is non-invasive and repeatable, aortic calcification on chest-XP was used as an index of atherosclerosis. No patients had evidence of calcified atherosclerosis at the start of hemodialysis therapy. The patients were divided into three groups according to vascular changes. Group 1 (20 patients) showed no calcification during the observation period. Group 2 (11 patients) had mild or moderate aortic calcification (thin linear aortic calcification). In group 3 (11 patients), massive and severe calcification was accelerated by hemodialysis. 18 parameters which might be considered to promote atherosclerosis were evaluated in each group. The age in group 3 was 53.8 +/- 10.4 (mean +/- standard deviation) years, which was older than the 42.1 +/- 12.6 year age in group 1 (p less than 0.025). Duration of dialysis in group 3 was 121.9 +/- 30.5 months, which was significantly longer than the 82.0 +/- 31.0 months in group 2 (p less than 0.01) and the 77.3 +/- 55.3 months in group 1 (p less than 0.025). Serum HDL-cholesterol levels in groups 2 (23.0 +/- 4.5 mg/dl) and 3 (20.9 +/- 6.6 mg/dl) were significantly lower than the 28.6 +/- 8.3 mg/dl in group 1, (p less than 0.025 and p less than 0.05, respectively). Serum parathormone-C level in group 3 was 14.7 +/- 8.6 ng/ml, which was significantly higher than the 6.1 +/- 6.0 ng/ml level in group 1 (p less than 0.01) and the 5.0 +/- 7.8 ng/ml level in group 2 (p less than 0.025). In discriminant analysis, age, duration of dialysis, hematocrit, serum HDL-cholesterol, parathormone-C, and alkaline phosphatase level were the independent factors used to distinguish the three groups. These findings suggest that 1) aging is a basal factor in the promotion of atherosclerosis, 2) hypo-HDL cholesterolemia is a major factor in the early phase of atherosclerosis, 3) hyperparathyroidism could have an important role in the late phase of atherosclerosis, 4) dialysis itself might promote atherosclerosis directly, and 5) blood pressure level is not major factor for atherosclerosis over a long observation period, at least in our study.
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PMID:Study on the atherosclerosis mechanism in chronic hemodialysis. 366 70

For comparison with our previous study on early calcification in human atherosclerosis, the aortas of rabbits and chickens with experimentally induced atherosclerosis were studied by gross examination, light microscopy and electron microscopy, including various cytochemical techniques. Nine male New Zealand white rabbits and nine male white leghorn chickens were fed an atherogenic diet of chow with 8% peanut oil and 2% cholesterol for one, two or three months. Six rabbits and six chickens, fed normal chow for one, two or three months, served as controls. The normal diet chickens were found to have lipid-negative spontaneous fibrous plaques in the abdominal aorta, which following atherogenic diet developed lipid deposition and increasing calcium deposition. The normal diet rabbits had no aortic lesions, but following an atherogenic diet developed highly lipid-positive foam cell intimal lesions which subsequently developed increasing amounts of smooth muscle cells and calcium. Ultrastructurally, the aortic plaques in normal diet chickens were composed of smooth muscle cells, collagen, elastic fibers, ground substance and a few small extracellular matrix vesicles bounded by a trilaminar membrane. In the atherogenic diet chickens, these vesicles increased in number as did their staining for calcium by the pyroantimonate technique. The membranes of vesicles were cytochemically positive for alkaline phosphatase and adenosine triphosphatase. Similar matrix vesicles were present in the interstitium of the media. In both intima and media, the vesicles appeared to be largely derived from degenerating smooth muscle cells. The aortas of atherogenic diet rabbits were similar to the chickens except for many more lipid-laden foam cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcification in atherosclerosis. II. Animal studies. 378 82

Matrix vesicles are widely regarded as the initial site of calcification in epiphyseal growth plate cartilage, in growing bone and in predentin. This opinion has recently been challenged on grounds that the early aqueous methods used for electron microscopic tissue preparation may have produced an erroneous picture by causing mineral dislocation. However, this argument has now been refuted by multiple investigators throughout the world using a variety of anhydrous methods coupled with electron probe analysis to show convincingly that matrix vesicles are, indeed, associated with initial mineral. Matrix vesicles appear to mineralize by concentrating calcium and phosphate at a protected site close to the inner leaflet of the vesicle membrane. Calcium may be attracted by its affinity for acidic phospholipids of the vesicle membrane, and phosphate may be concentrated by the action of transmembrane phosphatases of the matrix vesicle membrane. Evidence is accumulating to suggest that alkaline phosphatase of the matrix vesicle membrane functions as a phosphotransferase or phosphate vector, transporting PO4 across the vesicle membrane. The mechanism(s) of matrix vesicle biogenesis are discussed including budding from the plasma membrane (for which there is much support), cell degeneration (for which there is gathering support), extrusion of intracytoplasmic vesicles (for which there is weak support), and extracellular subunit self-assembly (for which there is little support). It is suggested that none of these mechanisms is necessarily exclusive, thus more than one mechanism may function in the same tissue. Finally, it is noted that in many calcific diseases, ranging from arthritis to atherosclerosis, mineralization is initiated by extracellular membrane-invested vesicles which are probably analogous to the matrix vesicles of skeletal tissues.
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PMID:Mineralization by matrix vesicles. 638 26

Using the alkaline phosphatase test, the authors studied the capillaries of 41 fields in clinically healthy people aged 22-64 years and animals (dogs, cats, rats) and also in individuals aged 45 to 64 years with mild atherosclerosis in the area of the median cerebral artery trunk. It has been established that unlike "normal" people, atherosclerotic patients of the respective age show an increase in the volume of deposited blood in the presence of a reduction of the working surface and the average indices of the activity of alkaline phosphatase leading to a considerable diminution (21.5-23.5%) in the intensity of metabolic processes.
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PMID:[Histochemical characteristics of the vascular-capillary bed of the brain during aging and in arteriosclerosis]. 647 21


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