Dietary Hypercholesterolemia Research Articles

Cytochemical correlates of atherosclerosis-resistant and susceptible lesions of the normal rabbit aorta

Quantitative cytochemical and microfluorimetric techniques were employed to compare mural intermediary metabolism—endothelial macromolecular uptake changes in spontaneous aortic-arteriosclerotic lesions of normolipemic New Zealand White rabbits. Specifically, mural succinic (SDH), lactic (LDH), and glucose-6-phosphate (G-6-PDH) dehydrogenase activities and luminal surface uptake of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were measured in lesion sites abnormally resistant (calcified) and susceptible (proliferative) to dietary hypercholesterolemia. Calcified lesions exhibited severe (55–66%) diminution of SDH, LDH, and G-6-PDH activities within the involved inner mural zone and a comparable (68%) decline in luminal FITC-BSA uptake. Concomitant reductions in FITC-BSA uptake (30%) and marker enzymes of the predominant energy transducing pathways in arterial tissue, i.e., SDH (30%) and LDH (31%), were evidenced in proliferative foci, whereas G-6-PDH was augmented (52%) in comparison to nonlesioned aortic segments. These data lend additional support to the concept that endothelial uptake of plasma-borne macromolecules is coupled to oxidizable substrate requirements of inner avascular compartments of the arterial wall. It is postulated that diminished macromolecular transport in these degenerative lesions stems from reduced mural metabolic demands, and that pharmacologic reduction of vascular smooth muscle metabolism may depress uptake of sclerogenic macromolecules.

ラットの食じ性高コレステロール血症に及ぼすスピルリナ（Ｓｐｉｒｕｌｉｎａ ｐｌａｔｅｎｓｉｓ）の影響

The Sprague-Dawley-strain rats were devided and classified into four groups: (1) the rats fed on the basal diets, (2) the rats fed on the basal diets containing 1% cholesterol, (3) the rats fed on the basal diets containing 16% spirulina, and (4) the rats fed on the basal diets containing 16% spirulina and 1% cholesterol.The results obtained were as follows. Elevation in total cholesterol, LDL+VLDL cholesterol, and phosholipids in serum caused by cholesterol feeding (Group 2) were reduced clearly by feeding (Group 4). Fall' in HDL cholesterol level caused by cholesterol feeding (Group 2) was reduced by feeding spirulina (Group 4). It was expected from these results that spirulina may prevent dietary hypercholesterolemia and arteriosclerosis. And, dietary hypercholesterolemia caused by cholesterol feeding was cured by spirulina feeding.The fatty liver caused by high-fat and high-cholesterol diets was also cured rapidly by feeding spirulina.

Lipid diffusibility in the intact erythrocyte membrane

The lateral diffusion of fluorescent lipid analogues in the plasma membrane of intact erythrocytes from man, mouse, rabbit, and frog has been measured by fluorescence photobleaching recovery (FPR). Intact cells from dystrophic, normoblastic, hemolytic, and spherocytotic mouse mutants; from hypercholesterolemic rabbits and humans; and from prenatal, neonatal, and juvenile mice have been compared with corresponding normals. The lateral diffusion coefficient (D) for 3,3'-dioctadecylindodicarbocyanine iodide (DiI[5]) in intact normal human erythrocytes is D = 8.2 +/- 1.2 X 10(-9) cm2/s at 25 degrees C and D = 2.1 +/- 0.4 X 10(-8) cm2/s at 37 degrees C, and varies approximately 50-fold between 1 degree and 42 degrees C. The diffusion constants of lipid analogue rhodamine-B phosphatidylethanolamine (RBPE) are about twice those of DiI[5]. The temperature dependence and magnitude of D vary by up to a factor of 3 between species and are only influenced by donor age in prenatals. DiI[5] diffusibility is not perturbed by the presence of calcium or local anesthetics or by spectrin depletion (via mutation). However, lipid-analogue diffusibility in erythrocyte ghosts may differ from intact cells. Dietary hypercholesterolemia in rabbits reduces the diffusion coefficient and eliminates the characteristic break in Arrhenius plots of D found in all other cells studied except frog.

Experimental studies on the hypolipidemic activity of chloridarol

The efficacy of chloridarol (2-benzofuryl-p-chlorophenyl carbinol) as hypolipidemic agent was evaluated in rats and rabbits. In normolipidemic rats chloridarol, at doses ranging from 50 to 200 mg/kg/day, decreased plasma triglycerides without affecting cholesterolemia and fast- or norepinephrine-induced lipolysis. The drug proved effective in reducing fructose-induced hypertriglyceridemia and dietary hypercholesterolemia in rats; in the latter model chloridarol significantly raised both the HDL cholesterol and the HDL/VLDL + LDL cholesterol ratio. In hyperlipidemic rabbits the drug had no effect on plasma cholesterol, but it lowered triglyceridemia. The action of chloridarol on rat liver ultrastructure was also investigated. Treatment for one month induced peroxisome proliferation, less marked, however, than that elicited by clofibrate; after a prolonged chloridarol treatment (9 months), this effect had almost completely disappeared and the ultrastructure of the hepatocytes was close to that of controls.

The effect of squalane on the absorption of dietary cholesterol by the rat.

Replacement of dietary triglyceride by a saturated hydrocarbon, squalane, resulted in a significant reduction (up to 50%) of cholesterol absorption of control values. Squalane may be useful in the treatment of dietary hypercholesterolemia.

Metabolism of very low density lipoproteins in diet induced hypercholesterolemic pigtail monkeys ( Macaca nemestrina)

Cholesterol-fed male pigtail monkeys were used to determine the metabolic mechanism of dietary hypercholesterolemia. Cholesterol feeding (200–400 mg/ day) in monkeys produced a moderate hypercholesterolemia, which progressed with time and after 15 months the plasma cholesterol levels were raised 8-fold. The initial rise in plasma cholesterol was due to an increase in low density lipoproteins (LDL), but later the increases in intermediate (IDL) and very low (VLDL) density lipoproteins were mainly responsible for the rise in plasma cholesterol. To determine the metabolic mechanism, animals, both before and after cholesterol feeding, were co-injected with 131I-labelled VLDL from normal and 125I-labelled VLDL from cholesterol-fed donors. The fractional catabolic rate of autologous VLDL apolipoprotein B, which decayed biphasically, depended upon the dietary status of the recipient animal. The decrease in fractional catabolic rate was due to more VLDL apolipoprotein B being metabolized by the slower second phase. Normal VLDL apolipoprotein B in cholesterol-fed animals was catabolized by the slower second phase to a greater proportion than that in normal animals, where it was mainly transferred to LDL.

Induction of aortic lipid deposition in a high-response (ExHC) rat fed a diet containing cholesterol and cholic acid

Male ExHC and Sprague—Dawley rats were fed a diet containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil for 16 weeks. The ExHC rat is highly susceptible to dietary hypercholesterolemia. Aortas of the ExHC rats showed Sudan-stained deposits and cholesterol accumulation in the intima and media, whereas no deposited lipids were seen in those of the Sprague—Dawley rats. In male and female ExHC rats fed diets containing the above supplements at 3 dose levels, plasma cholesterol and aortic lipid deposition were found to be dose-dependent. Lipid deposition was more prominent in females than in males, but aortic intimal proliferation was absent.

Effects of egg yolk and moctamide on serum lipids in man.

Forty‐one healthy male volunteers received 9 egg yolks daily in addition to their ordinary meals for 14 days. Mean elevation of serum cholesterollevels was 21,6 mg per 100 ml (11.4%) of the initial level. Middle‐aged men (40 to 45) showed more elevation of serum cholesterollevel than young men (18 to 20). After the first egg yolk fee ding period, 6 young men and 3 middle‐aged men, whose serum cholesterol levels increased by more than 10%, were selected to examine the etfect of moctamide on dietary hypercholesterolemia. They were given a daily oral dose of 300 mg of moctamide during the second egg yolk feeding period of 2 weeks, which was started 4 to 8 weeks after the end of the first period. In the third period, they were given 150 mg per day of moctamide in the same way. Daily doses of 300 mg of moctamide completely inhibited the elevation of serum cholesterol, while 150 mg suppressed it significantly.

Letter: Wastefulness of beef-rich diet.

Comments1 July 1974Wastefulness of Beef-Rich DietA. JARRELL RAPER, M.D., F.A.C.P.A. JARRELL RAPER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-1-124_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial "Expensive Beef: A Blessing in Disguise?" (Ann Intern Med 80:547-549, 1974) makes the points that (1) Americans eat much more beef than they really need for nutrition; (2) this is expensive and (3) the high saturated-fat (beef) diet may be contributing to our "national dietary hypercholesterolemia," with appropriate implications for development of vascular disease.Missing, however, were the larger implications of our "beef rich" diet in terms of the world food situation now in the process of a sharp deterioration in supply. The startling fact is that the American beef-rich diet is very wasteful of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical College of Virginia Health Sciences Center Richmond, Virginia 23219 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1974Volume 81, Issue 1Page: 124-124KeywordsDietFoodNutritionVascular diseases Issue Published: 1 July 1974 PDF DownloadLoading ...

Genetic studies on induced and spontaneous hypercholesterolemia in rats.

Weanling Sprague-Dawley rats of both sexes were fed a high cholesterol diet for 7 days. They were then divided into groups of high responders or low responders according to their plasma cholesterol levels. By the above selection and repeated sibmating within high responders of the same generation, progeny of both sexes became progressively more susceptible to dietary hypercholesterolemia. These rats have tentatively been given the short name ExHC and have at present been bred to the F10 generation. Some, but not all, male ExHC rats develop spontaneous hypercholesterolemia on a basal low cholesterol diet.

The hypocholesterolemic action of eritadenine in the rat

The hypolipidemic properties of eritadenine, an adenine derivative isolated from the Japanese mushroom Lentinus edodes, were investigated in rats with an emphasis on the effect on plasma cholesterol. Eritadenine lowered all the plasma lipid levels (cholesterol, triglyceride and phospholipid) and it was more than 10 times as active as clofibrate when administered in the diet. Large oral doses of eritadenine produced a hypocholesterolemic effect 3 hours after administration. Plasma free cholesterol was more affected than esterified cholesterol. Parenteral routes of administration did not seem to be as effective as the oral route. Dietary hypercholesterolemia was also suppressed by eritadenine. The acute Triton-induced hyperlipidemia was slightly suppressed by eritadenine, but proportionally less than in the normal rat. Although adenosine showed no effect on the hypocholesterolemic action of eritadenine, a twenty-fold excess of adenine may have interfered with the action of eritadenine.

Acutely-induced dietary hypercholisterolemia in the rat

Acutely-induced dietary hypercholisterolemia in the rat

Anti-hypercholesterolemic action of scleroglucan and pectin in chickens.

SummaryPectin and the polysaccharide scleroglucan reduced dietary hypercholestero-lemia in chicks; this reduction was accompanied by an increased excretion of chloroform-methanol extractable lipid, including cholesterol. The chemical dissimilarity of pectin and scleroglucan suggests that the anti-hyper-cholesterolemic activity of the two materials may be due to their physical rather than to their chemical properties.

Cholesterol flux into aorta in experimental nephrosis.

SummaryConcentrations of cholesterol and phospholipid in plasma lipoproteins, rates of cholesterol influx into the aortic wall, and concentration of cholesterol in the aorta have been measured in rats with hypercholesterolemia induced by diet or by experimental nephrosis. Nephrotic hypercholesterolemia was due primarily to an increase in the lipoproteins of density < 1.006; the cholesterol/phospholipid ratio was moderately increased in this fraction and in the fraction of density 1.006–1.063. Mild dietary hypercholesterolemia was associated with an increase in the latter fraction and with marked increases in the C/P ratio of the low and very low density fractions. Severe dietary hypercholesterolemia was due to increases in all fractions though the major increase was still in the fraction of density 1.006–1.063. The rate of cholesterol influx was most closely related to the concentration of cholesterol in this fraction. Among animals with dietary hypercholesterolemia, there was a significant relation betwe...

A Study of the Hypocholesterolemic Activity of the Ethyl Esters of the Polyunsaturated Fatty Acids of Cod Liver Oil in the Chicken: I. Effect on Total Serum Cholesterol

This report is concerned with the polyunsaturated fatty esters of cod liver oil and their effect on total serum cholesterol in hypercholesteremic chickens. An ethyl ester fraction of cod liver oil (I no. 315) was found 4 times as effective as natural cod liver oil (I no. 160) in lowering total serum cholesterol in the hypercholesterolemic chicken. Increasing the iodine number of the ethyl ester preparation to 374 increased the hypocholesterolemic activity approximately twofold. An ethyl ester fraction of menhaden oil was found equal in hypocholesterolemic activity to an equivalent ethyl ester fraction of cod liver oil. The hypocholesterolemic effect of the polyunsaturated fatty esters is related to the degree of unsaturation of the fatty esters fed. This hypocholesterolemic effect of the fish oils was obtained only during the period that they were fed. When the oils were withdrawn from the ration, hypecholesterolemia returned. Dietary hypercholesterolemia diminished with age.

The Role of Local Cholesterol Reutilization in Atherogenesis

The prevention and treatment of spontaneous atherosclerotic lesions presents one of the most challenging clinical problems to internists, surgeons, and pathologists, since our knowledge of the pathogenesis of the basic alterations of the arterial wall is at present fragmentary and ill-defined. Since the early work of Anitschkov²on the production of experimental lesions in the rabbit, after prolonged dietary hypercholesterolemia, that have some resemblance to those found in man, and the high concentration of cholesterol in the early spontaneous plaque, a natural relation between disturbances in lipid metabolism and atherogenesis has been suspected.^5,6,14 Recent emphasis on studies of local factors in this disease has been the direct result of efforts to reconcile extensive data on aberrations of the blood lipid spectrum with the histochemical and morphological changes encountered in early atheroma, since a satisfactory correlation between specific lipid changes and the degree of atherosclerosis present in many clinical