Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys.

A semipurified diet containing 1.2 mg of cholesterol/Cal was fed to cynomolgus monkeys (Macaca fascicularis). At the end of 6 months, a group of 18 animals was killed for evaluation of atherosclerosis in the aorta and the coronary arteries. The remaining monkeys were assigned to three groups of 18 animals each and fed, during the following 18 months, semipurified diets containing 0.34 mg of cholesterol/Cal with or without alfalfa meal, or a diet consisting entirely of Monkey Chow. a decrease in cholesterolemia and plasma phospholipid levels, normalization in the distribution of plasma lipoproteins, and reduction in the extent of aortic and coronary atherosclerosis were observed in monkeys fed the semipurified diet containing alfalfa, although the intake of cholesterol remained as high as in the usual American diet. These changes, also observed in monkeys fed a chow diet almost devoid of cholesterol, suggest that alfalfa counteracts the atherogenic effect of dietary cholesterol.     

The influence of dietary olive oil and margarine on aortic cholesterol accumulation in cholesterol-fed rabbits maintained at similar plasma cholesterol level.

The present study compares the atherogenicity of a standard diet and diets with 10% olive oil or 10% margarine added, in rabbits maintained at a mean plasma cholesterol level of about 20 mM for 13 weeks. Each group consisted of 15 animals. The distribution of cholesterol in plasma between VLDL, IDL, LDL and HDL was similar in the 3 groups. The thoracic aortic cholesterol accumulation was 16.6 +/- 1.6, 11.4 +/- 1.0 (P < 0.05) and 12.6 +/- 1.7 (P > 0.05) nmol/mg wet weight for the group receiving standard diet, diet with 10% olive oil added and diet with 10% margarine added, respectively. There was no significant difference between groups in the occurrence of the atherosclerotic changes in the proximal and distal parts of coronary arteries, abdominal aorta and renal arteries. The occurrence of atherosclerotic changes in the pulmonary arteries was equal in the groups receiving standard diet and diet with 10% margarine added while it was significantly lower (P < 0.05) in the group receiving diet with 10% olive oil added. The atherosclerotic changes at the aortic orifice of coronary arteries were quanticated morphometrically and were most severe in the group on the standard diet. The results indicate a comparable atherogenic effect of 10% olive oil or margarine addition to standard diet on development of atherosclerosis in rabbits maintained at a similar plasma cholesterol level. The study also suggests that supplementation of olive oil or margarine to standard rabbit diet leads to lower cholesterol accumulation in the thoracic aorta compared with standard diet, an effect not modulated by changes in plasma cholesterol concentrations.     

Very early aortic responses during atherosclerosis induction in rabbits: measurement by duplex ultrasound. I. Non-invasive study of aortic hyperresponsiveness to serotonin

We report the use of a non-invasive ultrasound method to visualize and measure changes in serotonin reactivity of the abdominal aorta during the early stages of atherosclerosis development. Studies were performed at 0, 4, 8, and 14 weeks in New Zealand white rabbits fed a diet enriched with 0.5% cholesterol. Change in systolic vessel diameter at each examination was compared with changes in rabbits fed a control diet or rabbits on a diet enriched with cholesterol plus a concentrated marine lipid. After 4 weeks on the diets, the abdominal aortae of rabbit fed the cholesterol-rich diet displayed an enhanced vasoconstriction to serotonin (P less than 0.01). The enhanced vasoconstriction was observed prior to visible morphologic changes, and progressed when restudied at succeeding examinations. Morphologic abnormalities became evident at 8 weeks in cholesterol-fed animals. Dietary supplementation with marine lipid, rich in polyunsaturated fatty acids, diminished the effect of the atherogenic diet on aortic vasoconstriction.     

Reduction in plasma glucose after lipid changes in mice fed fish oil, docosahexaenoic acid, and eicosapentaenoic acid diets

BACKGROUND/AIM: Effects of the dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and fish oil on weekly changes in plasma glucose, total cholesterol, triacylglycerol, and phospholipid concentrations of male Crlj:CD-1 mice were investigated. METHOD: Animals were fed five different experimental diets which contained 6.0% lard (lard diet), 6.0% fish oil (fish oil diet), 1.5% DHA-ethyl ester+4.5% lard (DHA diet), 0.4% EPA-ethyl ester+5.6% lard (EPA diet), and 1.5% DHA-ethyl ester+0.4% EPA ethyl ester+4.1% lard (DHA+EPA diet) for 17 weeks. Glucose and lipid concentrations in plasma collected at weeks 0, 1, 2, 4, 6, 8, 12, and 16 were measured. RESULTS: Plasma phospholipid concentrations were significantly lower in mice fed the fish oil and DHA+EPA diets than in those fed the lard diet at week 2. Plasma total cholesterol and glucose concentrations were significantly lower in the fish oil diet group than in the lard diet group at weeks 6 and 8, respectively. CONCLUSION: These results indicate that the decreases in plasma glucose concentrations in response to intakes of DHA and EPA in mice take place over a longer period of time than similar decreases in the plasma lipid concentrations.     

Comparison of experimental hypercholesterolemia and atherosclerosis in male and female mini-pigs of the G?ttingen strain

The susceptibilities of male and female mini-pigs of the G?ttingen strain to experimental hyperlipoproteinemia and atherosclerosis were studied and compared. Hyperlipoproteinemia was induced in groups of pigs of each sex by adding 11.2% egg yolk and 0.5% cholesterol to the diet. The initial increase in the plasma cholesterol concentration was significantly greater in the female animals than in the male ones. In both sexes most of the increase in plasma cholesterol was referable to the low-density lipoprotein fraction. As the experiment proceeded, the difference in the plasma cholesterol level between the sexes became less pronounced. After 18 months on the lipid-rich diet the animals were slaughtered and examined for atherosclerotic lesions. Specimens from the coronary arteries and the thoracic and abdominal aorta were taken for lipid analyses. From colour photographs of the intimal surface of the aorta, the percentage area of visible atherosclerosis in the abdominal part was calculated. Atherosclerotic lesions were present in the coronary arteries and in the abdominal aorta in both sexes. In the abdominal aorta, the results of the lipid analyses, and the calculated percentage area of atherosclerosis, indicated that the degree of atherosclerosis was similar in male and female pigs. In the coronary arteries, the atherosclerosis was more pronounced in the female pigs, as judged from the accumulation of cholesterol.     

Hypercholesterolemia and aortic glycosaminoglycans of rabbits fed semi-purified diets containing sucrose and lactose

This study was designed to evaluate the role of dietary sucrose and lactose in a semipurified diet as initiating factors for aortic glycosaminoglycan (GAG) and lipid changes. Rabbits were fed sucrose or lactose as 40% by weight of a semi-purified, cholesterol-free diet for 10 weeks. At the end of the feeding period there was no macroscopic evidence of atherosclerosis. Sucrose-fed rabbits had significantly higher plasma cholesterol and phospholipid levels than the lactose-fed rabbits and triglyceride levels were variably elevated in the sucrose group. Analysis of plasma lipoproteins indicated that sucrose elevated VLDL and LDL when compared to lactose. Only the higher molecular weight form of apo B (apo BH) could be demonstrated when apo B components of isolated lipoproteins were analyzed. Sucrose-fed rabbits had significantly more aortic cholesterol, cholesteryl ester and phospholipid and tended to have more GAG/mg dry defatted aorta than the lactose-fed rabbits. Plasma cholesterol levels correlated with aortic lipids and in the sucrose group, aortic cholesteryl ester and cholesterol were strongly correlated with aortic GAG particularly hyaluronic acid. Results suggest that the semi-purified diet alters aortic GAG composition but in order for the initiation of cholesterol accumulation a significant increase in plasma lipoprotein cholesterol is necessary.     

Diet-induced atherosclerosis in cynomolgus monkey aorta and regression by the sixth-month observation.

Pathomorphologic analysis was employed to evaluate diet-induced atherosclerosis in cynomolgus monkey aorta and regression by administration of a hypolipidemic agent for six months after the atherogenic ration. Twenty-seven male cynomolgus monkeys were divided into three groups. Group A was fed individually with a high-fat diet containing 0.3% cholesterol under identical conditions for six months. Group B was fed with normal monkey chow for six months after the same atherogenic ration. Group C was fed with normal monkey chow and administered a hypolipidemic agent 1% of 4-[2-(4-isopropylbenzamido)ethoxy] benzonic acid for six months after the same atherogenic ration. Each thoracic and abdominal aorta of animal models was separately analyzed. Lipid composition analysis and esterified cholesterol (CE) in aortic wall, ratio of free cholesterol to phospholipid, surface involvement, and atherosclerotic index after Sudan IV staining were studied for evaluation of progression and regression. The configurations of atherosclerotic involvement were histologically evaluated among each group. These observed lesions, features specific to cynomolgus lesions, mainly consisted of lipid-rich foam cells, lipid debris, and proliferated extracellular matrix. No different lesion composition was noted between the thoracic and abdominal aorta. This may suggest that some local factors play an important role for development of atherosclerosis after the initial event. Group C had remarkable reduction of foam cells and of CE accumulation in both the thoracic and abdominal aortic wall. Accelerated regression in group C as compared with group B was demonstrated both biochemically and pathohistologically. These results suggest that substantial regression of atherosclerosis in both the thoracic and abdominal aorta can be expected. This hypolipidemic agent exerts notable antiatherosclerotic activity, along with a lowering effect on plasma total cholesterol levels.     

The effect of vitamin E, probucol, and lovastatin on oxidative status and aortic fatty lesions in hyperlipidemic-diabetic hamsters

Diabetes mellitus is associated with an increased risk of premature atherosclerosis, which may be due in part to an increased rate of low density lipoprotein (LDL) oxidation. Previous studies have shown that vitamin E, probucol, and lovastatin can reduce the oxidative susceptibility of LDL in normoglycemic animal models; however, few studies have investigated this in conjunction with aortic fatty streak lesion formation in diabetic hyperlipidemic models. Forty-eight Syrian hamsters were made diabetic by intraperitoneal injection of low dose streptozotocin. Diabetic animals (12 animals/groups) received a high saturated fat and cholesterol diet for 12.5 weeks. At 2.5 week of dietary treatments, the diet was supplemented with either: (1) 500 IU/day vitamin E (D+E); (2) 1% probucol w/w of the diet (D+P); (3) 25 mg/kg lovastatin (D+L); or (4) diabetic control (D). An age-matched group of hamsters (n=6) receiving the same diet but not made diabetic (ND) was used as control. At the end of the study, aortic arch foam cell-rich fatty streak lesion, plasma glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), phospholipids, alpha-tocopherol, plasma lipid peroxide and the susceptibility of LDL to copper-catalyzed oxidation were determined. Diabetes increased plasma glucose, and when combined with an atherogenic diet resulted in a further increase of plasma lipids. Vitamin E, probucol, and lovastatin significantly reduced plasma TG in the diabetic hamsters fed the atherogenic diet. Vitamin E treatment increased TC, probucol reduced HDL-C without affecting TC; whereas lovastatin reduced TC and selectively decreased non-HDL-C, and significantly reduced fatty streak lesion formation in the aortic arch. While vitamin E and probucol were effective in reducing several indices of oxidative stress including plasma lipid peroxides, cholesterol oxidation products and in vitro LDL oxidation, they had no effect on fatty streak lesion formation. Our results indicate that the LDL in diabetic animals is more susceptible to oxidation than in non-diabetic hamsters and that not only vitamin E and probucol but also lovastatin provide antioxidant protection. It appears that in this combined model of diabetes and hypercholesterolemia, progression of fatty streak lesion formation is mainly associated with changes in TC and non-HDL-C as affected by lovastatin, and is less dependent on the extent of LDL oxidation, changes in plasma TG level and oxidative stress status.     

疏水性表面活性剂对家兔实验性高脂血症及动脉硬化的预防作用

本文将22只家兔随机分为三组。喂饲胆固醇诱发高脂血症。实验组给予疏水性表面活性剂Soluchorol,探讨其对高脂血症及动脉硬化的预防作用。结果表明,实验组血清总胆固醇及低密度脂蛋白均明显低于高脂组(P<0.01)。血清过氧化脂质亦低于高脂组(P<0.05)。二组主动脉斑块面积及厚度的对比分析均有显著性差异。提示疏水性表面活性剂具有一定的降血脂及预防动脉硬化的作用。但对Soluchorol的合成过程及其在机体内的代谢过程,使用剂量及毒性,试验等方面尚需进一步研究。     

Effect of aging on fatty streak formation in a diet-induced mouse model of atherosclerosis

Age is considered to be a major risk factor for atherosclerosis, but it is unclear whether age has a direct effect on susceptibility to atherosclerosis. Wild-type mice develop fatty streak lesions in the aortic root only when fed a cholate-containing high fat/cholesterol diet. To investigate the influence of age on fatty streak formation, young (10 weeks) and old (53 weeks) female C57BL/6 mice were fed an atherogenic diet containing 15% fat, 1.25% cholesterol and 0.5% sodium cholate for 12 weeks. Atherosclerotic lesions at the aortic root were measured after cryosections were stained with oil red O. Results showed that old mice developed a comparable size of aortic lesions with young counterparts (5,600 +/- 2,480 vs. 6,457 +/- 1,537 microm2/section; p = 0.77), although old mice had significantly higher plasma cholesterol levels than young mice on the atherogenic diet (p < 0.05). Plasma levels of soluble vascular cell adhesion molecule 1 were significantly higher in old mice than in young mice on both chow and Western diets (p < 0.005). These data indicate that age has no direct effect on atherosclerosis susceptibility although it is accompanied by elevations in plasma cholesterol and vascular cell adhesion molecule 1 levels in C57BL/6 mice. Thus, increased cardiovascular events with age are probably related to a progressive increase in plaque size rather than to an increase in atherosclerosis susceptibility.     

Increase of serum high density lipoprotein with progression and regression of aortic lipid deposition in rats.

The progression and regression of aortic lipid deposition was studied in male ExHC rats. Rats in the progression group were fed an atherogenic diet containing 2% cholesterol, 0.4% sodium cholate and 10% olive oil for periods up to 32 weeks. Rats in the regression group were first fed the atherogenic diet for 16 weeks, and then maintained on a basal low cholesterol diet. Half the rats were killed at 4 weeks and the other half at 16 weeks after cessation of the atherogenic diet. Rat aortas of the progression group contained progressively more lipid pari passu with the duration of cholesterol feeding, but connective-tissue proliferation was absent. Deposited lipid in the aorta of cholesterol-fed rats disappeared very slowly after the rats were returned to the basal diet. serum HDL decreased in the hypercholesterolemic ExHC rats fed the atherogenic diet for 4 weeks. By contrast, serum HDL and apo A-I increased in both hypercholesterolemic ExHC rats fed the atherogenic diet for 32 weeks and slightly hypercholesterolemic ExHC rats fed the basal diet for 16 weeks in the regression period.     

A casein variant in cow's milk is atherogenic

Casein is a major protein in cow's milk that occurs in several variant forms, two of which are beta-casein A1 and beta-casein A2. The levels of these two proteins vary considerably in milk dependent on the breed of cow, and epidemiology studies suggest that there is a relationship between their consumption and the degree of atherosclerosis. In the present study, the direct effect of consumption of beta-casein A1 vs beta-casein A2 on atherosclerosis development was examined in a rabbit model. Sixty rabbits had their right carotid artery balloon de-endothelialised at t=0, divided randomly into 10 groups (n=6 per group), then for 6 weeks fed a diet containing 0, 5, 10 or 20% casein isolate, either beta-casein variant A1 or A2, made up to 20% milk protein with whey. Some groups had their diets supplemented with 0.5% cholesterol. Blood samples were collected at t=0, 3 and 6 weeks and rabbits were sacrificed at t=6 weeks. In the absence of dietary cholesterol, beta-casein A1 produced significantly higher (P<0.05) serum cholesterol, LDL, HDL and triglyceride levels than whey diet alone, which in turn produced higher levels than beta-casein A2. Rabbits fed beta-casein A1 had a higher percent surface area of aorta covered by fatty streaks than those fed beta-casein A2 (5.2+/-0.81 vs 1.1+/-0.39, P<0.05) and the thickness of the fatty streak lesions in the aortic arch was significantly higher (0.04+/-0.010 vs 0.00, P<0.05). Similarly, the intima to media ratio (I:M) of the balloon injured carotid arteries in A1 fed animals (0.77+/-0.07) was higher than in those that consumed A2 (0.57+/-0.04) or whey (0.58+/-0.04), but this did not reach significance. In the presence of 0.5% dietary cholesterol, the thickness of the aortic arch lesions was higher (P<0.05) in 5, 10 and 20% casein A1 fed animals compared with their A2 counterparts, while other parameters were not significantly different. It is concluded that beta-casein A1 is atherogenic compared with beta-casein A2.     

Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition

Results from several atherosclerosis studies using morphometric procedures have proven controversial with regard to whether over-expression of human LCAT in transgenic (Tg) mice is atherogenic. The purpose of the present study was to determine the effect of 10-fold over-expression of human LCAT on aortic free and esterified cholesterol (EC) deposition as well as plasma lipoprotein cholesteryl ester (CE) fatty acid composition in mice fed an atherogenic diet containing cholic acid. C57Bl/6 (control) and human LCAT-Tg mice were fed chow or an atherogenic diet (15% of calories from palm oil, 1.0% cholesterol and 0.5% cholic acid) for 24 weeks before measurement of aortic cholesterol content. Compared with the chow diet, control and LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in plasma total, free and EC, a 7-fold increase in plasma apoB lipoprotein cholesterol, and a 40-50-fold increase in hepatic cholesterol content. The aortic EC content was increased in control (0.7 vs. 1.2 mg/g protein) and LCAT-Tg (0.3 vs. 1.5 mg/g protein) mice fed the atherogenic diet compared with those consuming the chow diet; however, there was no difference in aortic free (14.4+/-6.8 vs. 18.5+/-7.7 mg/g protein) or esterified (1.2+/-1.0 vs. 1.5+/-1.2 mg/g protein) cholesterol content between atherogenic diet-fed control and LCAT-Tg mice, respectively. LCAT-Tg mice fed the atherogenic diet had a 2-fold increase in the ratio of saturated+monounsaturated to polyunsaturated CE species in plasma apoB lipoproteins compared with control mice (9.4+/-2.4 vs. 4.9+/-0.7). We conclude that over-expression of human LCAT in Tg mice fed an atherogenic diet containing cholic acid does not result in increased aortic cholesterol deposition compared with control mice, even though the CE fatty acid saturation index of plasma apoB lipoproteins was doubled.     

Consumption of Nonfat Milk Results in a Less Atherogenic Lipoprotein Profile: A Pilot Study

Background: An increase in plasma low-density lipoprotein (LDL) is a well-known risk factor in the development of atherosclerosis. Dairy consumption may lower the risk of atherosclerosis; however, studies on the effects of milk on cardiovascular risk factors are still scarce. We were interested in investigating whether the intake of milk improves the atherogenic lipoprotein profile. Aims: We investigated the effects of consuming whole or nonfat milk on plasma lipoprotein composition in healthy Japanese subjects as a pilot study. Methods: Normolipidemic subjects consumed 500 ml of whole milk (whole milk group; n = 7) or nonfat milk (nonfat milk group; n = 7) every day for 2 weeks. Results: The consumption of nonfat milk resulted in a lowering of plasma triglyceride (TG) and phospholipid levels and TG level in high-density lipoprotein (HDL) and increased the plasma apolipoprotein (apo) C-III level. In addition, the TG/cholesterol ratios in HDL and LDL were significantly decreased, and LDL particles became larger. In contrast, the only changes observed following whole milk consumption were increases in the plasma levels of apoC-III and apoE. Conclusions: These findings suggest that consumption of nonfat milk, but not whole milk, may result in a less atherogenic lipoprotein profile, and that the constituents of nonfat milk may improve lipid metabolism.     

Cardiac sarcoplasmic reticulum. Effects of an atherogenic diet during the neonatal and juvenile period

The effect on the cardiac sarcoplasmic reticulum of an atherogenic (1% cholesterol) diet fed during the neonatal vs the juvenile period of life was studied in Yorkshire swine. Male piglets were randomly assigned at birth to 1 of 4 groups: group I (control), group II (lactation feeding), group III (juvenile period feeding) and group IV (lactation and juvenile feeding). All animals were killed at 55 weeks of age and cardiac sarcoplasmic reticulum (SR) isolated for assay of calcium uptake, Ca2+-Mg2+ ATPase activity, and lipid analysis by thin-layer chromatography and gas chromatography. The amount of cholesterol/mg SR protein and the cholesterol/phospholipid ratio were higher in the animals fed during lactation (groups II and IV) and lower in those fed only during the juvenile period (group III). Phospholipid fatty acid patterns as measured by gas chromatography were unaltered in any group. Calcium uptake was markedly diminished in all experimental conditions: group II 47%, group III 65% and group IV 96%. Compared to the observed changes in calcium transport, the ATP hydrolytic activity was relatively less affected. Only in group IV a significant decrease (41%) was seen. Groups II and III show no change in ATP hydrolytic activity. The decrease in calcium uptake and altered cholesterol/phospholipid ratio without effect on ATP hydrolytic activity is consistent with an uncoupling of calcium transport related to the atherogenic diet in early life.     

Effect of enhancement of cholesterol degradation during neonatal life of guinea pig on its subsequent response to dietary cholesterol.

The effect of feeding cholestyramine to neonatal guinea pigs on their subsequent plasma cholesterol levels and response to dietary cholesterol were studied. Male neonatal guinea pigs were suckled for 6 days. One group was maintained on a 1.1% cholestyramine diet for 6 weeks and the control group weaned normally. Both groups of guinea pigs were then fed a standard diet of Guinea Pig Chow for 6 weeks. During the standard diet period bile acid and neutral sterol excretion rates were significantly higher in the group previously treated with cholestyramine than the control group despite the similarity in plasma cholesterol levels. When both groups of guinea pigs were subjected to a 0.5% cholesterol diet for 4 weeks, plasma cholesterol levels were significantly lower in the group previously treated with cholestyramine than the control group. The plasma cholesterol levels continued to be significantly lower in the group previously treated with cholestyramine after an additional four weeks on standard diet. These results suggest that stimulation of cholesterol catabolism in the neonatal period can influence the subsequent response to dietary cholesterol.     

Effects of feeding fish oil on the properties of lipoproteins isolated from rhesus monkeys consuming an atherogenic diet

This study examined plasma lipids and lipoproteins of rhesus monkeys fed fish oil incorporated into a highly atherogenic diet containing saturated fat and cholesterol. The animals were fed diets containing 2% cholesterol and either 25% coconut oil (group I), 25% fish oil/coconut oil (1:1; group II), or 25% fish oil/coconut oil (3:1; group III) for 12 months (n = 8/group). Adding menhaden fish oil to the diet increased plasma eicosapentaenoic acid and docosahexaenoic acid and decreased plasma linoleic acid in animals fed the fish oil containing diets. Plasma concentrations of all lipoprotein fractions were decreased in the fish oil groups. VLDL isolated from group I animals exhibited beta-mobility on agarose gels but the VLDL from groups II and III animals did not. The group I VLDL was more highly enriched in cholesteryl ester than was VLDL from groups II and III. Group I LDL had a small but significant increase in cholesteryl ester content compared to group III LDL. No differences in HDL composition were observed in the 3 groups. At least 6 times less apo E was recovered in VLDL, IDL, and LDL from group III animals than from group I animals. Assuming 1 molecule of apo B per lipoprotein particle, there were 50% fewer VLDL, IDL, and LDL particles in group III than in group I animals. Group III also had significantly lower molar ratios of apo E/apo B in VLDL, IDL, and LDL than did group I animals. When VLDL from all 3 groups were incubated with J774 macrophages at equal protein concentrations, only the VLDL from the group I animals stimulated cholesterol esterification. Thus, introducing fish oil into an atherogenic diet reduced the number of VLDL, IDL and LDL particles in plasma by as much as 50%, reduced the cholesteryl ester content of the circulating lipoprotein, and reduced the ability of the VLDL to stimulate cholesterol esterification in macrophages.     

Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens

Experimental evidence was sought concerning whether soy phytoestrogens (SPEs) inhibit postmenopausal atherosclerosis progression/extent and, if so, their effectiveness relative to traditional estrogen replacement therapy. Premenopausal cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce atherosclerosis. After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added. SPE effects on plasma lipids were better than those of CEE (higher high density lipoprotein cholesterol and no increase in triglyceride). Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE treatment partially inhibited (P = 0.10) the progression of atherosclerosis (common iliac artery atherosclerosis before and after treatment). CEE-treated monkeys had much less coronary artery atherosclerosis than the controls (P = 0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE significantly reduced the extent of common carotid and internal carotid artery atherosclerosis, and the two treatment groups were not significantly different.     

Fatty acid and lipid composition of the monkey retina in diet-induced hypercholesterolemia

We determined the fatty acid composition of the lipids of cynomolgus monkey retina in animals fed commercial chow or a saturated fat, cholesterol-enriched atherogenic diet for 100 days. Dososahesaenoic acid (22 :6) accounted for 25.8% of the ethanolamine phosphoglyceride fatty acids, 17.6% of the serine plus inositol phosphoglyceride fatty acids, 8.4% of the choline phosphoglyceride fatty acids and 5.8% of the neutral lipid fatty acids in the retinas of the chow-fed animals. Therefore, monkey retinas, like those of other mammalian species, ordinarily contain large amounts of 22 : 6. Retinas from the monkeys fed the atherogenic diet contained less 22 : 6 as well as other polyunsaturates in each of the phospholipid classes. The decrease in polyunsaturates was compensated for by increases in palmitic, stearic, and oleic acids. There was no difference in the amount of phospholipid, the distribution of phospholipid classes, or the amount of cholesterol in the retinas of the monkeys fed the atherogenic diet. These results indicate that the single type of lipid alteration produced in the retina by a diet enriched in saturated fat and cholesterol is a decrease in the polyunsaturation of the retinal phospholipids. The reduction in retinal 22 : 6 content might have significance for photoreceptor function.     

ATP结合盒转运子A1与动脉粥样硬化(2)

ATP结合盒转运子A1(ABCA1)在血清脂蛋白代谢及细胞胆固醇平衡的维持中起重要作用。贫脂的载脂蛋白A-I是ABCA1介导的磷脂/胆固醇流出的接受体。ABCA1可以通过将胆固醇从肠壁吸收细胞运至肠腔而调节胆固醇的吸收,肠道ABCA1mRNA含量与胆固醇吸收呈负相关。不饱和脂肪酸减少非脂化胆固醇和磷脂的流出,而饱和脂肪酸没有这种作用。动脉硬化饮食15周后,ABCA1转基因鼠主动脉硬化明显减少。