Journal of atherosclerosis research最新文献

The effects of calcium on cholesterol metabolism have been examined in 6 patients. The age of the subjects ranged from 61–73 years. Five of the patients were osteoporotic. The calcium was administered as organic salts (calcium glycerophosphate or calcium gluconogalactogluconate) and as dried skimmed milk.

The results show that increased calcium in the organic form caused increased excretion of faecal bile acids and faecal total fat. There was no change in faecal neutral steroid output; increased faecal cholesterol was compensated by decreased coprostanol excretion. When the calcium was given in the form of skimmed milk, faecal bile acids and faecal fat remained elevated. Faecal excretion of cholesterol continued to rise and was accompanied by the return of faecal coprostanol output almost to the basal level, resulting in increased total neutral steroid excretion.

The serum cholesterol and triglyceride levels showed little change from the basal levels during the calcium supplementation periods.

Heparin resistance was found to be higher in a group of elderly people with a history of coronary or cerebral thrombosis than in a group of apparently healthy people of similar age. Heparin resistance in both these groups was higher than in a group of healthy younger people. Plasma fibrinogen concentration was correlated with heparin resistance.

The plasma fibrinogen concentration and the heparin precipitable fraction of plasma was raised in the elderly subjects. “Fibrinogen B” was present in a high proportion of the elderly subjects and it is suggested that this is identical with the heparin precipitable fraction of plasma. The erythrocyte sedimentation rate was also increased in the elderly subjects.

Acid mucopolysaccharides (MPS) and glycoproteins from the intima and the media of 26 Japanese thoracic aortas were studied with emphasis on ageing and atherosclerosis.

Total acid MPS significantly increased with age in the intima and slightly in the media; they decreased in both layers in the presence of atherosclerosis. Cellulose acetate electrophoresis was used to separate acid MPS into three fractions for analysis, namely hyaluronic acid, heparitin sulphate and chondroitin sulphates B and/or C. Changes in the compositional pattern of acid MPS with ageing or atherosclerosis were inconclusive.

The total carbohydrate fraction of aortic intimai glycoproteins decreased until the age of 60 years, and increased thereafter, while the fraction from the media tended to increase progressively with age. The most conspicuous change in glycoprotein constituents in atherosclerosis was the marked fall in intimai sialic acid.

Galactose, mannose and f ucose were identified as integral components of vascular glycoproteins in all preparations examined. However, an additional chromatographic spot that corresponded to glucose was detected in 2 cases.

Daily UV-irradiation of male guinea pigs fed a high-cholesterol, high-saturated fat diet caused no differences in skin sterols, but the amount of cholesterol in the liver, lungs, adrenals and intestine was significantly increased in the irradiated animals. Irradiation was associated with a decrease in epididymal fat weight and diminution of esterified fatty acids in this tissue and in the liver; the level of this fraction in serum was higher. Cholesteryl esters in epididymal fat showed a shift from monoenes to saturated fatty acids. Microscopic examination of the aorta and myocardium revealed a higher degree of atherosclerotic changes in irradiated animals. Since our previous reports on irradiated rats fed a low-cholesterol diet indicated a decrease in liver cholesterol with an increase in skin sterols, it is concluded that the effect of UV-light may be dependent on the dietary fat composition, the extent of the exogenous cholesterol intake and the rate of endogenous sterol synthesis.

Following the injection of tritiated 17β-estradiol into male survivors of myocardial infarction and men apparently free from complications of atherosclerosis, urine was collected and assayed for estrone, 17β-estradiol, estriol, and 3H associated with these fractions. Estradiol production rate (E₂PR) was derived. Urinary testosterone, total 17-ketosteroids, serum cholesterol, phospholipid and plasma triglyceride were determined. The survivors of infarction had significantly higher mean cholesterol, phospholipid and total lipid than the controls. No significant difference was observed between the control and infarction groups in the urinary excretion of estrone, estradiol, estriol, testosterone and 17-ketosteroids but the coronary patients had a reduced mean E₂PR. Cholesterol increased with urinary estradiol and E₂PR in the infarction group and with the E2PR/testosterone ratio in the control group. Phospholipid increased with testosterone, estradiol and E₂PR in the infarction group. Triglyceride increased with estriol and the sum of the 3 estrogens in the infarction group and with estrone, estradiol, estrone/testosterone ratio and estradiol/testosterone ratio in the control group. The increased serum lipid levels in the infarction group may have contributed to their coronary sclerosis but no evidence that estrogen tended to normalize the serum lipid pattern was obtained.

Alimentary-induced lipaemia was studied in 10 young men after the ingestion of 1 g fat/kg body weight. The plasma triglycerides were separated into three fractions in a density gradient, in which one of the fractions contained the chylomicrons. It was found that after the meal both the plasma triglycerides of exogenous and endogenous origin increased. The importance of this finding is discussed.

In vitro cholesterol esterification by either human or rabbit’s aorta in the presence of β-fatty acid-labelled lecithin appears to depend on a lecithin:cholesterol fatty acid (acyl) transferase. The activity of this enzyme increases in human fatty atherosclerotic lesions and in atherosclerotic aortas from cholesterol-fed rabbits. Activity decreases in fibrous and calcified human atherosclerotic lesions.

It has been shown that addition of saturated fat to a semi-synthetic ration is atherogenic for rabbits, whereas addition of the same amount of fat to rabbit chow has no effect. To test the factor in the chow which may exert this "protective" action, we fed rabbits the following diets: (SS): semi-synthetic containing 14% hydrogenated coconut oil; (SS-PF): semi-synthetic containing 12% hydrogenated coconut oil (HCNO) and 2 % of the fat extracted from rabbit chow; (XP-HCNO): the fat-extracted chow residue plus 14 % HCNO; and (PC-HCNO): chow milled with additional 12 % HCNO. Another group of rabbits was fed the semi-synthetic diet augmented with 1 % lauric acid (SS-LA) to ascertain if the atherogenicity of free fatty acids would be evident in a semi-synthetic diet as it has been in rabbits fed cholesterol. One chow-fed group of rabbits (PC) served as control. After 6 months of feeding it was found that all the groups of rabbits fed diets containing HCNO had elevated liver cholesterol levels and elevated liver ester cholesterol. The groups fed the semi-synthetic diet (SS, SS-PF and SS-LA) had elevated serum cholesterol levels (200-250 mg/100 ml), elevated serum β-lipoprotein cholesterol levels and cho-lesterol/phospholipid ratios greater than 1.00. They all exhibited marked atherosclerosis. Group XP-HCNO had moderately elevated serum cholesterol levels (64 mg/ 100 ml as compared to 40 mg/100 ml in the normal rabbits), elevated serum ^-lipoprotein cholesterol and a C/PL of 1.21, but atheromata in this group were minimal. The group fed chow and 12% HCNO (PC-HCNO) exhibited no abnormalities in its serum lipid spectrum and no atheromata. The data suggest that the complete chow is required to overcome the effects of HCNO on serum lipids, but the extracted chow residue will inhibit aortic atherosclerosis, at least over a 6-month feeding period. The pattern of liver and serum lipids suggest that in animals fed HCNO there is an initial increase in liver cholesterol, followed by increases in serum total and β-lipoprotein cholesterol, and then by aortic plaque formation. Cholesterol biosynthesis from [l-14C]acetate was inhibited in most of the groups fed HCNO, eliminating in- creased cholesterogenesis as a mechanism for the moderate hypercholesteremia which we observed.

Esterase activity has been examined in the aorta of rats given hyperchol-esterolaemic, thrombogenic or atherogenic diets, and rabbits given an atherogenic, semi-synthetic diet low in cholesterol.

In normal rat aorta, the specific activity values are in the numerical order of phospholipase A > lipase > cholesterol esterase. In the rabbit the activities were in the same order but of much lower magnitude.

In the rat, feeding an atherogenic diet containing 40 % peanut oil, 5 % cholesterol and 2 % cholic acid produced an increased phospholipase A and lipase, and a decreased cholesterol esterase activity compared with normal animals. Replacement of peanut oil with butter produced no change in phospholipase A and cholesterol esterase and only a small increase in lipase. Thiouracil depressed the higher lipase and abolished the increased phospholipase A activity of the peanut oil group, and decreased cholesterol esterase in both the butter and peanut oil groups.

In rabbits given the semi-synthetic low cholesterol diet for 10 and 32 weeks, a decrease in phospholipase A and cholesterol esterase activity was seen compared with normal animals. An increased lipase activity was seen at 10 weeks but not at 32 weeks.

It is concluded that the high lipase and low cholesterol esterase activity in the peanut oil fed rat, and the low cholesterol esterase activity in the semi-synthetic diet fed rabbit may be contributing factors in the dietary production of atherosclerosis in these two species.