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M B Megan

Publications and source records attributed to M B Megan.

13 recordsLinked to original sources
PubMed1987

Arterial uptake indices of low density lipoproteins after fatty streak formation in Cynomolgus monkeys.

To evaluate changes in arterial wall uptake of an atherogenic lipoprotein in early atherogenesis the uptake of labelled low density lipoprotein was measured in four segments of aorta in Cynomolgus monkeys with diet induced fatty streaks. The influx rate of low density lipoprotein was estimated from a simple kinetic model. The mean influx rate, expressed as plasma equivalents of tracer, was 69 nl.cm-2 per hour in fatty streak monkeys and 28 nl.cm-2 per hour in controls (p less than 0.001). Using additional assumptions, provisional estimates of the rates of apparent efflux were calculated. In fatty streak monkeys the mean apparent efflux rate, relative to the accumulation of tracer in the wall, did not differ significantly from the efflux rate in controls (8.7% per hour vs 7.9% per hour, p greater than 0.05). Thus intimal permeability to low density lipoprotein is increased at the fatty streak stage of lesion formation but apparent efflux may not be changed. The data fit the hypothesis that relative failure of efflux is a major cause of excess low density lipoprotein accumulation in the vessel wall in hypercholesterolaemia.

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PubMed1986

Lipid metabolism in xanthomatous skin of hypercholesterolemic rabbits.

The authors studied xanthomatous skin in cholesterol-fed rabbits for changes in lipid content and in activities of enzymes regulating intracellular lipid content. After 80 days of hypercholesterolemic diet, xanthomas were widespread and changes in lipid metabolism were marked. In both tissue homogenates and cell membrane pellets, unesterified cholesterol and phospholipids increased 2-fold to 6-fold, and cholesteryl esters increased about 30-fold. Tissue triglycerides, however, decreased to half the levels found in control skin. Cholesterol esterification rates, measured by activity of acyl coenzyme A: cholesterol acyltransferase, increased moderately to markedly; hydrolase activity against 4-methylumbelliferyl oleate also increased at both acid and neutral pH, but hydrolase activity against cholesterol oleate increased only at acid pH. Thus, hypercholesterolemia caused striking increases in intracellular cholesterol esterification rates, increases in lipase activity at both neutral and acid pH, and increases in cholesteryl ester hydrolase activity at acid pH. Increases in cholesterol-esterifying activity uniformly exceeded increases in cholesteryl ester hydrolytic activity in congruence with net accumulation of cholesteryl ester. Skin xanthoma grade, however, had no consistent relation to the cholesterol esterification rates. Instead, the enzyme data suggested that marked abnormalities of lipid metabolism are diffusely distributed through dermal tissue as a precondition for the focal emergence of xanthomas.

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PubMed1985

A defect in mobilization of cholesteryl esters in rabbit macrophages.

Macrophages provide an important way for cholesteryl esters to accumulate in tissues in pathologic amounts. We studied cholesteryl ester metabolism in thioglycollate-induced peritoneal macrophages obtained from normocholesterolemic and hypercholesterolemic rabbits. The macrophage preparations from normocholesterolemic rabbit (MN cells) had 26 nmol esterified cholesterol/mg cellular protein, incorporated 1 nmol of labeled oleate into cholesteryloleate/2 h per mg cellular protein and had an acyl-coenzyme A:cholesterol acyltransferase activity of 22 pmol cholesterylpalmitate formed/min per mg protein in isolated membranes. The macrophage preparations from hypercholesterolemic rabbits (MHC cells) contained a 12-fold greater mass of cholesteryl ester, had an 8-times higher rate of formation of cholesteryloleate, and had 3-times more acyl-coenzyme A:cholesterol acyltransferase activity in the isolated membranes. When a cholesterol acceptor (10% fetal bovine serum or 10 mg of lipid-free fetal bovine serum protein) was added to the culture medium of rabbit MHC cells, the MHC cells retained more than 70% of their cholesteryl esters after 48 h of incubation. In contrast, when a cholesterol acceptor (10% fetal bovine serum) was added to the medium of thioglycollate-induced, cholesterol-enriched macrophages from mice, the mice macrophages retained only 19% of their cholesteryl esters after 48 h of incubation. The limited capacity of rabbit macrophages to release unesterified cholesterol from stored cytoplasmic cholesteryl esters to an exogenous acceptor may be related to the propensity of rabbits to develop atherosclerotic lesions.

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PubMed1983

The effect of diet on plasma carnitine, triglyceride, cholesterol and arterial carnitine levels in cynomolgus monkeys.

Plasma carnitine, cholesterol, and triglycerides were measured over a 13-week period in male cynomolgus monkeys (M. fascicularis) that were fed a control diet (Purina Monkey Chow, n = 5) and a semisynthetic hypercholesterolemic diet (n = 15). Plasma cholesterol levels rose from 100 +/- 5 to 743 +/- 50 mg/dl in the cholesterol-fed group during the 13-week period but remained below 133 +/- 13 mg/dl in the control group. Plasma triglyceride levels tended to be lower in the cholesterol-fed group, particularly at 4 week (28 +/- 3 vs 42 +/- 7 mg/dl, P less than 0.05). Plasma carnitine levels rose from 43 +/- 4 to 53 +/- 5 nmol/ml within two weeks in the cholesterol-fed group and remained above control values for the duration of the study. Carnitine levels were significantly higher in the carotid arteries of cholesterol-fed animals relative to control (224 +/- 25 vs 109 +/- 15 pmol/mm in situ length, P less than 0.01). Higher mean values of carnitine were also found in iliac, subclavian, and coronary arteries of cholesterol-fed animals but not in femoral arteries.

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PubMed1980

Arterial platelet accumulation in experimental hypercholesterolemia.

Accumulation of arterial platelets was calculated from 51Cr radioactivity in the intima-inner media of flushed, perfuse-fixed aortas and branch vessels of cynomolgus monkeys 48 hours after labeling of the blood platelets. In normo-cholesterolemic controls the radioactivity per square centimeter of tissue was consistently higher in aortic branching sites (circumostial aorta) than in the remainder of the aorta. In monkeys given 10 and 100 days of hypercholesterolemic diet radioactivity rose in circumostial aorta in proportion to increases in streaks and in areas of Evans blue uptake. In branch artery inner wall, where intimal changes were minimal and usually absent, counts were significantly greater in animals given 100 days of hypercholesterolemic diet than in controls. After 10 days of hypercholesterolemic diet the mean radioactivity in aortic branch artery inner wall uniformly exceeded control values, but usually nonsignificantly, permitting the speculation that changes in platelet-intima interactions may occur in widespread fashion throughout the arterial tree very early in hypercholesterolemia when lesion formation is incipient or absent.

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PubMed1978

The relation of hypercholesterolemic fatty streaks to intimal permeability changes shown by Evans blue.

The aortic localization of diet-induced fatty streaks in relation to focal increases in intimal permeability was evaluated in cynomoglus monkeys. Animals fed a hypercholesterolemic diet and studied at 10, 15, and 100 days had increasing intensity of Evans blue dye uptake. The overlap of fatty streaks with areas of dye intake increased as the areas of dye uptake enlarged, but all hypercholesterolemic groups showed some fatty streaks not topographically related to areas of dye uptake or flow instability. Because the upper thoracic aorta tended to show more advanced fatty streak formation dissociated from evident permeability change or hydraulic instability, it is suggested that mechanical factors associated with the geometric configuration of the descending thoracic aorta may have a significant role in the localization of some hypercholesterolemic fatty streaks.

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PubMed1975

Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets.

Fibrous proteins were measured in five arterial beds in adult cynomolgus monkeys after administration of atherogenic and regression regimens. Atherosclerosis was induced by feeding the monkeys a hypercholesterolemic diet containing 1.2% cholesterol for 17 months. A low-fat, cholesterol-free regression diet was then given for 60 days, 200 days, and 20 months. In atherosclerosis, collagen concentration (mg/g dry weight) and collagen content (mg/cm length of artery) both increased. At 200 days of regression the collagen concentration, but not the collagen content, was higher than it was in atherosclerosis. In late regression (20 months), the collagen content was lower than it was in atherosclerosis, although in the five arterial beds considered together the collagen concentration was not significantly lower. Both the elastin concentration and the elastin content rose in atherosclerosis and decreased in regression. These mass data suggest that fibrous proteins are lost from the arterial wall during a regression regimen. Correlative evidence suggests that younger intimal fibers may be chiefly susceptible to fibrolytic activity, leaving dense intimal scars characteristic of regressed arteries.

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PubMedDate not supplied

Structural and hemodynamic response of peripheral arteries of macaque monkeys to atherogenic diet.

The arteries of monkeys given atherogenic diets develop marked intimal thickening and medial thinning, but luminal size apparently changes minimally. The hemodynamic significance of the atherosclerotic changes is therefore uncertain. To evaluate vascular function in atherosclerotic arteries, we studied the hind-limb vessels of adult male rhesus and cynomolgus monkeys to assess the structural and hemodynamic responses to an atherogenic diet given for about 1.5 years or for much longer periods (6.5 years for rhesus and 4.3 years for cynomolgus monkeys). The intimal cross-sectional area greatly increased after the atherogenic diet, but there was no significant luminal narrowing after either the 1.5-year diet or the longer diet periods. The media of atherosclerotic arteries showed focal atrophy and focal thinning after pressure fixation, but the total medial mass was not decreased even after the long diet periods. Hemodynamic studies indicated mild functional impairment in the atherosclerotic vessels; resting resistance increased and vasodilator responses decreased, but adrenergic responses were preserved. Thus, the marked changes that occur in the arterial wall in experimental primate atherosclerosis include adaptations to lesion formation that permit a long prestenotic phase of atherosclerosis in which vascular dysfunction is minimal.

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