Journal of atherosclerosis research最新文献

The relationship between diffuse intimal thickening and zonal loss of medial enzyme activity was studied in 23 human aortas, from the 1st to the 10th decade of life, by means of the NADH-tetrazolium reductase-Van Gieson histoenzymic method. This relationship, together with the relationship to lipid accumulation, was examined with the histoenzymic NADH-TR and ATPase-Oil Red 0 methods in the aorta, coronary, internal carotid, middle cerebral, femoral, popliteal, axillary and brachial arteries in a fuither 8 subjects.

At a critical intimal thickness of 0.15 mm the aortic media showed enzymic loss in its middle zone. In the other arteries examined this critical intimal thickness for medial enzyme loss varied from 0.2–0.45 mm. Intracellular lipid (the “fatty streak”) was noted in some relatively unthickened intimas, where the tunica media showed no enzyme loss. Extracellular diffuse intimal lipid was only observed where enzyme activity was impaired in the tunica media. In a few cases diffuse intimal thickening and medial enzyme loss were seen in the absence of intimal lipid accumulation.

These results support the hypothesis that progressive diffuse intimal thickening over-extends nutritional perfusion from the lumen to the inner and middle zones of the tunica media. The resulting failure of energy-producing metabolism in the media would impair the local synthesis of lipotrophic agents (phospholipid and protein) that are required for transporting cholesterol. Reduced outward transport of cholesterol would lead to the accumulation of cholesterol in the inner arterial layers, as in atherosclerosis.

Guinea pigs with varying intakes of ascorbic acid (0.5, 5 and 50 mg per 24 h) were receiving an atherogenic diet with addition of 0.3 % cholesterol during 140 days. In guinea pigs with a chronic deficiency of vitamin C (0.5 mg for 24 h) a significantly higher accumulation of cholesterol in liver, adrenal glands and small intestine was observed in comparison with the group receiving 50 mg of vitamin C for 24 h. Concentrations of cholesterol in the same organs of the group receiving 5 mg of vitamin C per 24 h were within these extreme data. A significantly negative correlation was confirmed to exist between cholesterol concentration in liver, adrenal glands and small intestine and saturation of tissues with vitamin C; with decreasing saturation of tissues with vitamin C, the accumulation of cholesterol in the relevant tissue was increasing. Cholesterol levels in brain and blood serum were not significantly influenced by differing intake of vitamin C. The most advanced atheromatous changes were found in aorta and coronary arteries of the hypovitaminous group (0.5 mg of vitamin C per 24 h). High doses of vitamin C (50 mg per 24 h) did not prevent the appearance of morphological changes in vascular system but only slowed down the process of atheromatous reconstruction.

The effects of 2,2,6,6-tetrakis(nicotinoyloxymethyl) cyclohexanol (K-31) on cholesterol-fed rabbits were compared with those of meso-inositol hexanicotinate and nicotinic acid.

In the regressive studies using oral K-31 after inducing experimental atherosclerosis, the drug suppressed the elevation of serum total cholesterol, phospholipid and triglyceride levels, and also decreased the deposition of total cholesterol and phospholipids in the liver. In the progressive studies, oral K-31 exhibited a marked serum cholesterol lowering effect.

The effect of K-31 on intestinal absorption of cholesterol was studied in thoracic-duct fistula rats administered labeled cholesterol. K-31 significantly depressed the absorption of [4-¹⁴C]cholesterol into lymph, and caused more absorbed [4-¹⁴C]-cholesterol to appear as ester.

The hypocholesterolemic action of K-31 is thought to be due to inhibition of exogenous sterol absorption.

• (1)

  Sodium [1-¹⁴C]acetate was sextensively incorporated into the lipid fractions of chick aortic cells in secondary cultures maintained as monolayers, indicating a linear relation between the incorporation rate and the incubation time over 8 h.

• (2)

  When laminaran sulfate was added to this culture system, at concentrations between 2.5 and 40 μg/ml culture medium for 24–72 h, it depressed lipid synthesis in aortic cells, as measured by [¹⁴C]acetate incorporation rates into the lipid fraction.

• (3)

  Inhibition of lipid synthesis depended on the concentration of laminaran sulfate and its incubation time; inhibition was greater in the neutral fat and free sterol fractions than in the phospholipid fraction.

• (1)

  The effect of dl-N-(α-methylbenzyl) linoleamide (MBLA) and its optically active isomers (d-MBLA and l-MBLA) on cholesterol metabolism was studied in rats. After administering MBLA, d-MBLA and l-BMLA with [4-¹⁴C]cholesterol, total [4-¹⁴C]cholesterol levels in the plasma and liver, and its ester ratio in the liver were markedly depressed after 4 h. After 8 h, the same results were obtained, and the esterified [4-¹⁴C]cholesterol ratio in the small intestine was also depressed, but there was no significant difference after 24 h. The inhibitory effect on plasma and liver [4-¹⁴C]cholesterol pools was in the order d-MBLA > MBLA > l-MBLA.

• (2)

  The cholesterol-lowering effect of MBLA was not decreased after administering it for 4 weeks.

• (3)

  After administering MBLA, d-MBLA and l-MBLA with [³H] cholesterol to thoracic-duct fistula rats, total [³H]cholesterol levels and its ester ratio in lymph were markedly depressed for 24 h. These results suggest that the cholesterol-lowering mechanism of these compounds is due to reduced cholesterol absorption from the intestines.

• (4)

  Hepatic cholesterogenesis was accelerated when a diet containing 0.1 % of MBLA was administered for 1–2 weeks. The acceleration of cholesterol biosynthesis by inhibitors of cholesterol absorption is considered to be due to a homeostatic mechanism that maintains body cholesterol via a feedback control.

The association of cigarette smoking and atherosclerosis was investigated in 747 autopsied men, 20–64 years of age. Aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested for validity and reliability on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. Data have been analysed with reference to total sample and also to subsamples grouped according to the presence or absence of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diabetes, stroke, etc.). Atherosclerotic involvement of aorta and coronary arteries is greatest in heavy smokers and least in nonsmokers. Occupational physical activity and educational level achieved did not account for observed differences in extent of lesions.

Incorporation of [³²P]phosphate into sphingomyelin, phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine of normal swine arteries was studied in vitro. Choline added to the media increased the specific activity in phosphatidyl choline, whereas ethanolamine had no significant effects. Addition of 2-amino-2-methyl-l-propanol in concentrations from 0.001–0.1 M inhibited incorporation of ³²P into all the phospholipid classes; phosphatidyl choline was affected to a somewhat greater extent than the others. Ratios of choline to aminomethylpropanol in the media of 1:1 and 10:1 resulted in partial reversal of the inhibition; the reversal was nearly complete at a ratio of 100:1. The pulmonary artery seemed to be somewhat less sensitive than the coronary artery to inhibition of net phospholipid synthesis by aminomethylpropanol.

Addition of 3-amino-l-propanol, dimethylaminoisopropanol and triethanol-amine in concentrations of 0.001, 0.01 and 0.1 M each resulted in inhibition of [³²P]-phosphate incorporation into the phospholipids of the coronary arteries; there was little evidence of specific inhibition of any of the individual phospholipid classes studied.

Four variations in molecular structure of the surfactant polyoxyethylene alkyl phenol formaldehyde polymer were synthesized, purified and tested for their ability to modify the severity of aortic atherosclerosis induced in rabbits by feeding cholesterol and trans isomerized olive oil for 84 days in comparison with a placebo-treated control group. The four molecular variations studied were the 20 and 30 oxyethylated n-decyl phenol formaldehyde polymers and the 20 and 30 t-octyl phenol formaldehyde polymers. After 84 days on the cholesterol-rich diet, all the serum lipid fractions of the control group and of the surfactant-treated groups were markedly elevated. In comparison with the control group, the severity of aortic atherosclerosis was much less in the groups treated with the oxyethylated t-octyl surfactants. In contrast, there was no significant reduction in the severity of atherosclerosis in the group treated with the 30-oxyethylated n-decyl surfactant. The reduction in severity of atherosclerosis in the group treated with the 20-oxyethylated n-decyl surfactant was relatively slight.

In 63 of 86 experiments there was a significantly greater release of free fatty acids when platelet-rich human plasma was incubated with coconut oil than when platelet-poor plasma was used. In 19 of 20 experiments fatty acid-poor albumin enhanced the lipolysis of coconut oil. The results of this study indicate that platelet-rich plasma and fatty acid-poor albumin should be used when endogenous plasma lipoprotein lipase activity is determined in vitro.

Adipose tissue from rats fed high fat diets were found to exhibit significantly less adrenaline-induced FFA release than those from rats maintained on low fat commercial diet.

Addition of CPIB to the high fat diet reversed this suppression of adrenaline-induced FFA release by isolated adipose tissue. Supplementation of the diet with cholesterol-cholate also reversed the suppressive effect of high dietary fat on adrenaline-induced lipolysis in vitro.

Adrenaline-induced FFA release in adipose tissue seems to depend upon the metabolic status of the tissue as determined by previous nutrition of the animal.