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)

The amounts of buffer- and Triton-extracted apo B (LDL-protein), as well as the sum of these two fractions, were correlated with the total tissue cholesterol and hydroxyproline content (as a measure of collagen) in grossly normal intima, fatty streaks, and fibrous plaques of human aortas obtained at autopsy. Quantitative values of buffer- and Triton-extracted apo B were obtained by sequentially extracting homogenates of aortic intima with an aqueous buffer and one containing Triton X-100, and measuring the apo B content in each extract by an electroimmunoassay relative to plasma LDL or Triton-treated LDL. Significant positive correlations were obtained between the following: tissue cholesterol and both buffer-extracted and total-extracted apo B in grossly normal intima; tissue cholesterol and Triton-extracted apo B in microdissected fibrotic caps and cores of fibrous plaques, as well as in whole plaques. A positive correlation was also obtained between tissue cholesterol and total-extracted apo B in the necrotic core. A significant negative correlation was found between Triton-extracted apo B and collagen in whole plaques. The calculated mean percent of total tissue cholesterol in the different aortic regions that could be present as part of an intact LDL particle were: 100% in grossly normal intima, 16% in fatty streaks, and 11% in fibrous plaques. The positive correlation between Triton-extracted apo B and cholesterol in plaques suggests one or both of the following: the extracellular pool of cholesterol or some material increasing concurrently with cholesterol interacts with apo B or another part of the LDL particle; or the apo B containing lipoprotein is trapped in the hydrophobic environment of extracellular lipid. Both possibilities would render the particle less soluble in aqueous buffers. The negative correlation between Triton-extracted apo B and tissue collagen and the lack of a significant correlation between buffer-extracted apo B and collagen content suggests that collagen is probably not responsible for apo B retention in the aortic intima.
Atherosclerosis 1979 Mar
PMID:Correlation in the human aorta of APO B fractions with tissue cholesterol and collagen content. 22 86

The in vitro activity of cholesteryl ester hydrolase preparations of rat and rabbit aortas was assayed in the presence of the taurine and glycine conjugates of cholic, chenodeoxycholic, deoxycholic and lithocholic acids or in the presence of Triton X-100 and Tween-20. Maximum activity was obtained with tauro- or glycocholic acids. As in the case of pancreatic cholesteryl esterase, trihydroxycholanoic acid derivatives may serve an obligatory function.
Atherosclerosis 1978 Nov
PMID:Aortic cholesteryl esterase. Influence of bile salts. 71 40

We investigated the effect of hyperlipidemic serum on cAMP accumulation in cultured smooth muscle cells from the rabbit aorta. The cells were grown to confluence, then cultured for 24 h in hyperlipidemic medium (total cholesterol: 2.2 mmol/l). cAMP accumulation was enhanced in response to isoproterenol 10(-6) M, as compared to control cells, and this enhancement was still detectable in the presence of IBMX 10(-3) M, a potent inhibitor of phosphodiesterase. Application of propranolol 10(-4) M at 5 min after isoproterenol showed a similar time course for cAMP disappearance. The phosphodiesterase activity in the 40 000 g supernatant of the Triton X-100 solubilized homogenates of the cells in hyperlipidemic medium remained unchanged. Beta-receptor assays showed an increased Bmax with a similar Kd, and such may contribute, at least in part, to the increased adenylate cyclase activity. An extended incubation in the presence of hyperlipidemic medium attenuated the cAMP accumulation, possibly due to excessive increases in the total cholesterol content.
Atherosclerosis 1985 Aug
PMID:Cyclic AMP accumulation in rabbit aorta smooth muscle cells altered in the presence of hyperlipidemic serum. 241 25

Injury to endothelial cells appears to be an important initial event in the pathogenesis of many diseases such as acute lung injury, venous and arterial thromboembolism, and atherosclerosis. Different methods for detecting damage to cultured endothelial cells have been described. However, their relative sensitivity as markers of endothelial cell damage has not been adequately determined. We compared the loss of 51Chromium (51Cr), the cytoplasmic enzyme lactate dehydrogenase (LDH), and 111Indium (111In) from endothelial cells upon exposure to several injurious agents. Cultured bovine pulmonary artery endothelial cells in confluent monolayers were labeled with 51Cr or 111Inoxine and exposed to increasing concentrations of the nonionic detergent, Triton X-100 (0.2 to 1%), hydrogen peroxide (1 to 500 microM), or neutrophils stimulated with phorbol myristate acetate. With all forms of injury, loss of 51Cr occurred earlier and to a greater extent than LDH loss which in turn was greater than loss of 111In. Substantial loss of 51Cr was observed in the absence of appreciable ultrastructural damage to endothelial cell external membranes. The findings may reflect the relative ease with which small molecules such as adenine nucleotides (51Cr-labeled) escape whereas larger molecules such as LDH and proteins binding 111In are retained intracellularly. Thus, 51Cr loss appears to be a more sensitive indicator of sublytic endothelial cell injury than either 111In or LDH release.
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PMID:Loss of 51chromium, lactate dehydrogenase, and 111indium as indicators of endothelial cell injury. 368 67

The properties of CDP-choline:1,2-diacylglycerol cholinephosphotransferase (CPT) (EC 2.7.8.2.), which catalyzes de novo synthesis of phosphatidylcholine, were studied in rat arterial wall. The optimal pH of CPT of the arterial wall was about 8.5. On subcellular fractionation of the arterial wall, the highest activity was found in the microsome-rich fraction; the cytosolic fraction showed only a trace of activity. The Michaelis constant (KM) for CDP-choline was 0.019 mM. The CPT activity of a homogenate of arterial wall increased linearly with increase in concentration of diolein up to 3.2 mM. 20 mM magnesium and 0.2 mM manganese ions caused marked activation respectively and essential for the activity. Calcium, barium, cobalt, copper, and ferrous ions were inhibitory. 0.5 mM ethylenediaminetetraacetic acid (EDTA) and 0.5 mM glycoletherdiamine-N,N,N'N'-tetraacetic acid (GEDTA) increased the activity in the presence of 10 mM magnesium ion. Sonication of the enzyme solution and addition of high concentration of detergent, such as Triton X-100 and Tween 20, markedly decreased the activity. Porcine liver phosphatidylcholine, phosphatidylethanolamine, and especially polyenephosphatidylcholine increased CPT activity of the arterial wall, while lysophosphatidylcholine was strongly inhibitory. The properties of arterial CPT activity under various conditions are discussed.
Atherosclerosis 1982 Jun
PMID:Studies on CDP-choline:1,2-diacylglycerol cholinephosphotransferase activity in rat arterial wall. 628 57

The concept that much of the cholesterol deposition in atherosclerotic plaque development is provided by ingress of blood-derived apo B-rich lipoproteins into the arterial intima is given support by the study of arterial apo B accumulation. To compare the arterial wall level of immunoreactive apo B during the progression of diet-induced atherosclerosis in two widely used animal models of atherosclerosis, rhesus and cynomolgus monkeys were fed an atherogenic diet for 4, 8, and 12 months and their abdominal aortas quantitated for apo B. Apo B was extracted from aortic intima-media homogenates in two forms: Tris-buffer extractable or 'loosely bounds' and detergent (Triton X-100) extractable or 'tightly bound'. The aortic extracts were quantitated for apo B by radial immunodiffusion, using goat anti-rhesus apo B along with serum LDL standards of the appropriate species diluted in the two extract solutions. The control monkeys' aortas contained only buffer-extractable apo B. The atherosclerotic aortas of both species of monkeys progressively increased their levels of loosely bound and tightly bound apo B through 4, 8, and 12 months of atherogenic diet feeding, with the 8- and 12-month cynomolgus aortas containing much larger amounts of apo B than the rhesus aortas. These differences in aortic apo B content could be accounted for by the greater rate at which the cynomolgus atherosclerotic lesions developed at the later time points. When the total lesion apo B levels were correlated with representative morphometrically-quantitated histopathologic sections of the homogenized aortas, a highly significant correlation was seen between the total aortic apo B values and both the absolute area of the intimal lesions and the total area of oil red O stainable lipid in the lesions (P less than 0.001). These data indicate that as atherosclerotic lesions become larger and richer in lipid with progression of the disease, the amount of apo B-associated lipoproteins which are deposited unmetabolized in the lesions increases. These lipoproteins are increased in both the tightly bound and loosely bound forms.
Atherosclerosis 1984 Mar
PMID:Apoprotein B quantification in rhesus and cynomolgus monkey atherosclerotic lesions. 671 74

Endogenous alpha-tocopherol of low density lipoprotein (LDL) particles exposed to ferrylmyoglobin (iron in the form of FeIV = O) vanishes as a function of myoglobin concentration. After alpha-tocopherol depletion, subsequent heavy lipid peroxidation is prevented by caffeic and p-coumaric acids, i.e., phenolic acids present in foods and beverages, by a mechanism involving the one-electron transfer reaction between the phenols and the ferrylmyoglobin, with formation of metmyoglobin and the corresponding phenoxyl radicals from caffeic and p-coumaric acids, as previously discussed. Caffeic acid delays alpha-tocopherol consumption when present before oxidation challenging and restores alpha-tocopherol when added halfway during the reaction. Conversely, p-coumaric acid accelerates the rate of alpha-tocopherol consumption when added either before or during the oxidation reaction. In LDL enriched with alpha-tocopherol, caffeic acid induces an inhibition period of oxidation longer than that expected from the sum of discrete periods characteristic of the phenolic acid and alpha-tocopherol. Surprisingly, p-coumaric acid decreases the peroxidation chain rate. Similar effects of these phenolic acids on alpha-tocopherol consumption were observed in a Triton X-100 micellar system, i.e., in the absence of a peroxidation chain reaction. Results suggest that caffeic acid acts synergistically with alpha-tocopherol, extending the antioxidant capacity of LDL by recycling alpha-tocopherol from the alpha-tocopherol radical (i.e., alpha-tocopheroxyl radical). By contrast, the phenoxyl radical from p-coumaric acid (produced by electron-transfer reaction between phenolic acid and ferrylmyoglobin) oxidizes alpha-tocopherol. However, in spite of alpha-tocopherol consumption, the exchange reaction recycling p-coumaric acid can still afford an antioxidant protection to LDL on basis of the chain-breaking activity of p-coumaric acid. These results emphasize the biological relevance of small structural modifications of phenols on the interaction with alpha-tocopherol in LDL. The significance of these results in the context of atherosclerosis is discussed.
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PMID:Two related phenolic antioxidants with opposite effects on vitamin E content in low density lipoproteins oxidized by ferrylmyoglobin: consumption vs regeneration. 748 1

Cardiac ischemia is associated with an impairment in long-chain fatty acid metabolism. We studied carnitine palmitoyltransferase (CPT) in left ventricular biopsies of 6 transplant recipients with ischemia due to atherosclerosis, 4 patients with dilated cardiomyopathy, and 5 donor hearts. Total CPT activity was not significantly different between the three groups (7.9 +/- 3; 6.7 +/- 2, and 8 +/- 3 nmol/min/mg noncollagenous protein). Residual CPT activity after inhibition by malonyl-CoA (0.4 mM) was 38 +/- 11, 36 +/- 5 and 38 +/- 7%. There were no difference in IC50 values. Residual CPT activity after the addition of the detergent Triton X-100 (0.5%) was 58 +/- 17, 54 +/- 2 and 50 +/- 8% (nonsignificant). Our results suggest that (i) total CPT activity and (ii) the sensitivity of the interaction of CPT I with its regulator malonyl-CoA are not affected by cardiac ischemia, and (iii) the ratio of CPT I to CPT II is not altered in cardiac ischemia.
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PMID:Carnitine palmitoyltransferase in patients with cardiac ischemia due to atherosclerotic coronary artery disease and in patients with idiopathic dilated cardiomyopathy. 912 47

Advanced mineralization can cause brittleness of aortic walls with decreased elasticity thereby causing the wall to rupture. Although the precise mechanisms of dystrophic calcification remain unknown, morphological evidence reveals the presence of mineral-associated vesicles in the lesions and defective bioprosthetic valves. In an attempt to demonstrate the calcifiability of the vesicles, small segments of human atherosclerotic aortas with calcified lesions were removed at autopsy and then digested in a crude collagenase solution to release vesicles. A differential centrifugation was then used to isolate calcifiable vesicles, which was precipitated at 300,000 x g for 20 min. An exposure of the vesicles to a calcifying medium containing physiologic levels of Ca2+, Pi, and 1 mM ATP caused Ca deposition in a vesicle protein-concentration dependent manner. The calcifiability of the vesicles was further demonstrated by electron microscopy. Fourier transform spectroscopic analysis of the deposited mineral revealed the presence of a hydroxyapatite phase, closely resembling the native form of mineral in atherosclerotic plaques. In addition, calcifiable vesicles were enriched in ATP-hydrolyzing enzymes including Mg2+ or Ca2+-ATPase and NTP pyrophosphohydrolase that may be involved in normal and pathological calcification. Triton X-100 at 0.01% abolished 80% of both ATPase activity and ATP-initiated calcification. A comparison of vesicles isolated from non-atherosclerotic and atherosclerotic aortas indicated that atherosclerotic vesicles tended to have higher calcifiability. These observations suggest that the calcifiable vesicles play a part in dystrophic calcification of aortas in atherosclerosis.
Atherosclerosis 1999 Apr
PMID:Isolation of calcifiable vesicles from human atherosclerotic aortas. 1021 64

Extraction of ECV304 endothelial cells in 1% Triton X-100 at 4 degrees C resulted in a detergent-insoluble pellet that contained 90% of the caveolin, 78% of the src family kinases and 99% of the annexin II. When detergent-treated cells were loaded beneath a 10-30% sucrose gradient the caveolin and a large proportion of the cellular cholesterol floated at a density of 1.09 g/cm3, characteristic of caveolae and glycosphingolipid-rich membranes. With extended centrifugation the src family kinases, which were initially associated with this floating material, sedimented to the bottom of the gradient. Annexin II remained on the bottom of the gradient under both centrifugation conditions. After 24-h incubation with oxidised low density lipoprotein (oxLDL) about 7.5% of the total sterol in the cells was replaced by 7-ketocholesterol, the major oxysterol found in oxLDL. The majority of this 7-ketocholesterol was found in the light membrane fraction on sucrose gradients. Under these conditions src kinase activity more than doubled in the Triton-resistant fraction, without changes in the concentration of src kinase protein. Introducing oxysterols directly into the medium bathing ECV304 cells for 1 h also modulated the activity of src family kinases in the detergent-resistant membranes. An elevation in activity was observed for 7-ketocholesterol while 7alpha-hydroxycholesterol, 7alpha-hydroxycholesterol and cholesterol epoxide all produced decreases in the background level of src kinase activity. We conclude that 7-ketocholesterol and possibly other components of oxLDL can equilibrate into glycosphingolipid-rich membranes and increase the activity of src kinases, possibly by interaction with caveolin.
Atherosclerosis 1999 Apr
PMID:Src family kinase activation in glycosphingolipid-rich membrane domains of endothelial cells treated with oxidised low density lipoprotein. 1021 69


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