Experimental atherosclerosis in swine: effect of dietary protein and high fat

Two groups of pigs each consisting of 6 animals were fed for 18 months on isocaloric amounts of an experimental diet with a high fat content and cholesterol but with widely different levels of protein (5% vs. 25% by weight of the diet). In addition, a third group consisting of 4 animals was maintained on normal stock diet to serve as control.Animals of the low protein group showed the maximal intimal surface area involvement with atherosclerotic lesions in the aorta and coronary arteries, and also the most severe among the three groups. No significant differences were noted in the extent and severity of lesions between the high protein-high fat fed animals as compared with the high protein-low fat fed controls. Lesions of the low protein group had a higher cholesterol content and a raised cholesterol:phospholipid ratio than those in the other two groups.Extremely low levels of dietary proteins seem to have had a promotive effect on the induction of atherosclerotic lesions by an atherogenic diet, whereas adequate levels of dietary proteins have had a protective influence. The precise mechanism by which varying levels of dietary proteins have such effects is not understood. It may possibly be related to the aberrations of lipid metabolism induced by extremely low levels of dietary proteins.     

Repercussions of raloxifen, tamoxifen and estrogen on aortic atherosclerotic lesions of female rabbits submitted to ovariectomy and hypercholesterol diet

BACKGROUND: The role of hormone-replacement therapy in decreasing the risk of cardiovascular disease in women has not been firmly established. Recent studies have shown that the selective estrogen receptor modulators raloxifene, and tamoxifene, posses hypolipidemic and antiatherogenic properties. METHODS AND RESULTS: Forty-three adult female rabbits were submitted to ovariectomy (moment 1). Three weeks after surgical recovery, they were grouped in five groups as follows (moment 2): control group (9)--normal diet; cholesterol group (8)--0.5% cholesterol added to diet; raloxifen group (8); tamoxifen group (9); estrogen group (9)--diet added by 0.5% cholesterol and 60 mg raloxifen, 20 mg tamoxifen or 0.625 mg equine conjugated estrogen. The animals from all groups were sacrificed after 13 weeks (moment 3) and the thoracic and abdominal aortas were studied. We collected digital images of the observed atherosclerotic lesions in the vessel lumen by means of a computerized method. We analyzed serum levels of total cholesterol and fractions (HDL, VLDL, and LDL), as well as triglycerides. Among the animals that received hyper cholesterol diet and medication, we noticed a reduction of the total area of atherosclerotic plaques in the tamoxifen (P < 0.05) or estrogen group (P < 0.05) compared to the cholesterol group. Serum levels of total, LDL- and HDL-cholesterol were higher for the raloxifen, tamoxifen, estrogen, and cholesterol (P = 0.0001). CONCLUSION: Female rabbits treated with a high cholesterol diet associated to tamoxifen or estrogen had a statistically significant reduction in aortic atherosclerotic plaques. Even though there was a significant increase in cholesterol levels, we did not find any correlation between cholesterol levels and degree of aortic atherosclerotic lesion.     

中链甘油三酯对小鼠胆固醇代谢和胆固醇7α-羟化酶表达的影响

目的：研究中链甘油三酯对小鼠胆固醇代谢的影响及可能的机制。 方法： 分别用AIN-93G配方饲料（BC），含1％胆固醇的AIN-93G配方饲料（Chol），含1％胆固醇和14%富含豆蔻酸的长链甘油三酯（LCT）的AIN-93G配方饲料（Chol＋LCT），含1％胆固醇和14％的中链甘油三酯（MCT）的AIN-93G配方饲料(Chol+MCT)喂养C57小鼠6周，每组15只。观察血清总胆固醇（TC）、肝脏胆固醇含量、机体总胆汁酸含量以及肝脏胆固醇7α-羟化酶（CYP7A1）的表达。 结果： Chol＋MCT组小鼠血清TC低于（P＜0.01）、肝脏胆固醇高于（P＜0.01）、机体总胆汁酸含量低于（P＜0.01）、CYP7A1表达低于（P＜0.01）Chol组小鼠；Chol＋MCT组小鼠血清TC低于（P＜0.01）、机体总胆汁酸含量以及CYP7A1 表达高于（P＜0.01）Chol+LCT组小鼠、肝脏胆固醇含量不变。 结论： MCT对机体胆固醇水平的影响与CYP7A1表达有关。     

Morphological effects of moderate diet and clofibrate on swine atherosclerosis

Early proliferative coronary atherosclerosis was produced in swine by feeding them a high-fat, high-cholesterol diet for 17 months, at which time one group of animals was killed (reference group), while the remainder was transferred for 12 months to a moderate diet that resulted in serum cholesterol levels of about 190 mg/100 ml. The moderate diet only did not decrease the size of coronary lesions, but prevented their progression. The addition of clofibrate therapy caused regression that involved a significant decrease in size, gross sudanophilia, and extent of calcification and the disappearance of foam-cell lesions. Resultant serum cholesterol levels appear to be more important than the amount of dietary cholesterol in the progression, prevention, and regression of swine coronary atherosclerosis.     

Lowering of lipid composition in aorta of guinea pigs by Curcuma domestica

Background

A short-term study was carried out using guinea pigs to determine the effects of Curcuma domestica on lipid composition in the serum and aorta.

Methods

Animals were given food pellets containing 4% (w/w) powdered rhizome of C. domestica in order to determine its effect on cholesterol, triglyceride and phospholipid levels in the aorta and serum. The animals were fed either a cholesterol free diet or a high cholesterol diet (2% cholesterol, w/w, in food pellet) in order to induce hypercholesterolemia.. After five weeks of this diet treatment, blood and aorta were taken for biochemical analysis and histological studies.

Results

C. domestica in the diet showed no significant effect on the levels of cholesterol, triglyceride and phospholipid in the serum and aorta of the cholesterol free diet animals. However, addition of C. domestica to a high cholesterol diet counteracted increases in the levels of cholesterol, triglyceride and phospholipid in the aorta. Histology studies showed less cholesterol deposits in the aorta of high cholesterol diet animals given C. domestica compared to the high cholesterol diet animals not given C. domestica supplement. C. domestica also had a lowering effect on triglyceride level in the serum of high cholesterol diet animals but showed no effect on serum cholesterol and phospholipid levels.

Conclusion

This study has shown that dietary intake of C. domestica decreased all lipid composition levels in the aorta and also the serum triglyceride level. In addition, C. domestica also reduced cholesterol deposition in the aorta of high cholesterol diet animals.     

高脂高胆固醇膳食对小鼠PPARα基因表达及机体胆固醇水平的影响

目的:探讨高脂高胆固醇膳食对肝脏PPARα基因表达及机体胆固醇水平的影响。 方法:7-8周龄健康C57小鼠75只，随机分为5组，分别饲以相应配方饲料。 结果:与胆固醇膳食（Chol）相比，胆固醇＋多不饱和脂肪酸膳食（Chol＋PUFA）可增加(P<0.01)小鼠血清总胆固醇(TC)，增加的部分主要集中在HDL-C，降低肝脏胆固醇含量（P<0.01）；胆固醇＋单不饱和脂肪酸膳食（Chol＋MUFA）小鼠血清TC不变，肝脏胆固醇含量降低（P<0.01）；胆固醇＋饱和脂肪酸（Chol＋SFA）膳食可明显增加(P<0.01)小鼠血清TC，增加的部分主要集中在LDL-C，增加肝脏胆固醇含量（P<0.01）；此外，Chol+PUFA 膳食组小鼠肝脏PPARα mRNA和蛋白表达均高于Chol组（P<0.01），Chol+MUFA和Chol+SFA膳食组小鼠肝脏PPARα mRNA表达均明显低于Chol组（P<0.01）。 结论:在胆固醇基础上添加PUFA可诱导PPARα mRNA和蛋白的高表达,添加MUFA、SFA则抑制PPARα mRNA的表达；PPARα基因表达的改变可能进一步影响机体胆固醇水平。     

Unusual resistance of the ground squirrel to the development of dietary-induced hypercholesterolemia and atherosclerosis

This study was designed to examine the apparently unusual resistance to atherosclerosis in the adult male ground squirrel. In one study, serum lipid and lipoprotein patterns and concentrations of ground squirrels were observed after feeding for 26 weeks with either rodent chow or rodent chow supplemented with cholesterol. These two groups were compared to a third group fed chow diet for three weeks, then killed for baseline values to distinguish between aging effects and those induced by cholesterol feeding. No outstanding changes in the concentration and patterns of the serum cholesterol, triglycerides, and lipoproteins were observed in any groups. A higher serum phospholipid concentration in cholesterol-fed animals compared to animals fed chow diet alone for three weeks suggested that the rise was associated with aging rather than diet. The predominant lipoprotein fraction in all three groups was high-density lipoprotein (HDL). No lesions were found in the coronary arteries or thoracic and abdominal aortas.In a second study a primate diet with 50% egg yolk was given for 1 year. This diet caused elevation of serum cholesterol and phospholipid levels, and increased HDL, which had an unusual ability to carry as much cholesterol as the low-density lipoprotein (LDL). However, no arterial lipid accumulation was observed. Light microscopic and ultrastructural studies of the coronary artery and aorta revealed nothing unusual, and in structure, they resembled those of other small rodents. The only striking finding was that very few degenerative aging changes were found in the aorta when compared to rats of a similar age. The study demonstrates that the ground squirrel does not develop marked hypercholesterolemia with cholesterol feeding and that the majority of the elevated levels of serum lipids, particularly cholesterol, are transported as α-lipoprotein. Both of these factors, plus the lack of degenerative aging changes in the arterial wall may play an important role in the resistance of this particular species to atherosclerosis.     

The influence of barley fibre on bile composition, gallstone formation, serum cholesterol and intestinal morphology in hamsters

Frequency of gallstones, concentration of bile acids and cholesterol in bile, concentration of cholesterol in serum, and structure of the small intestinal mucosa were analyzed in male Syrian Golden hamsters fed a stone provoking fibre-free diet with or without supplementation of brewer's spent grain (BSG), a concentrated barley fibre source from the by-product of brewing. A significantly lower frequency of gallstones was found in the animals with 10% BSG dietary supplementation. Addition of 30% BSG after an initial 6-week period with a fibre-free, stone provoking diet seemed to dissolve previously formed gallstones. Total bile acid concentration was higher in bile from animals given a diet supplemented with 10% BSG. In addition, the cholesterol concentration in both serum and bile was lower in the 30% BSG supplemented group. Structurally, a 10% BSG supplementation decreased ileal epithelium height whereas a high supplementation (30%) of BSG induced a decrease in epithelial height both of jejunal and ileal mucosa. The results show that BSG has significant effects on the metabolism of bile acids and cholesterol as well as on the morphology of the small intestinal mucosa.     

Comparative primate atherosclerosis: I. Tissue Cholesterol Concentration and Pathologic Anatomy

Stump-tailed macaques (Macaca arctoides), African green monkeys (Cercopithecus aethiops), squirrel monkeys (Saimiri sciureus), and woolly monkeys (Lagothrix lagothricha) were fed control, solid atherogenic (1 mg cholesterol/cal) or liquid diets containing 0, 0.5, or 1 mg cholesterol/cal.Stump-tailed macaques fed the solid atherogenic diet had the highest tissue and serum cholesterol concentration (about 700 mg/dl) and the most extensive atherosclerosis. These monkeys appeared to respond differently to diets containing 1 mg cholesterol/cal. Those animals fed the liquid diet had higher liver cholesterol concentration but lower serum cholesterol concentration than animals fed the solid diet. African green monkeys fed the solid atherogenic diet had serum cholesterol concentrations of about 450 mg/dl. A greater percentage of the abdominal aorta was covered by plaque than the thoracic aorta. Coronary artery atherosclerosis was focal with the largest plaques being found in the left main coronary artery. The microscopic appearance of these plaques was similar to that of plaques from people.Squirrel monkeys fed the atherogenic diet were the most variable group. The average serum cholesterol concentration averaged about 450 mg/dl (range: 291 to 716). The percentage of aorta covered by plaque ranged from 0 to 55% with more thoracic than abdominal aortic atherosclerosis. There were findings consistent with hemorrhage in plaques from two animals. These monkeys, like stump-tailed macaques but unlike African green monkeys had relatively high liver cholesterol concentrations.Woolly monkeys appeared to develop atherosclerosis when fed 1 mg cholesterol/cal but did not have greatly elevated serum cholesterol concentrations.     

Dietary fish oil enhances monocyte adhesion and fatty streak formation in the hypercholesterolemic rat.

Using the rat model of atherosclerosis, the influence of dietary fish oil on early stages of atherosclerotic lesion formation was studied. Normocholesterolemic rats (serum cholesterol less than 100 mg/dl), moderately hypercholesterolemic rats fed cholesterol and cholic acid (serum cholesterol less than 400 mg/dl), and severely hypercholesterolemic rats fed cholesterol, cholic acid, and 2-thiouracil (serum cholesterol greater than 900 mg/dl) had their diets supplemented with 5% (w/w) "MaxEPA" fish oil for a period of 2 weeks. In each diet group safflower oil was used as a control for fish oil. Monocyte adhesion to the thoracic aorta and intimal foam cell formation were used to measure the extent of atherosclerotic lesion formation in each rat. Cholesterol and triglyceride levels were measured in both plasma and lipoprotein fractions. In normocholesterolemic rats, fish oil did not influence the morphology of the vessel wall. In moderately hypercholesterolemic rats, monocyte adhesion was the same irrespective of dietary oil, however, intimal foam cell formation was 2-fold higher in the fish oil-fed animals despite a reduction in serum cholesterol levels when compared to the safflower oil-fed animals. In severely hypercholesterolemic rats, monocyte adhesion to the vessel wall and intimal foam cell formation were both 4-fold higher in the fish oil compared with the safflower oil fed animals. These observations could not be attributed to differences in the plasma or lipoprotein profiles of safflower oil vs. fish oil fed rats. The results of this study suggest that dietary fish oil, when fed to hypercholesterolemic rats for a period of 2 weeks, enhances the rate of monocyte adhesion and fatty streak formation in the thoracic aorta.     

Effects of nutrition of disease and life span. II. Vascular disease, serum cholesterol, serum thromboxane, and heart-produced prostacyclin in MRL mice.

Mice of the autoimmune strain MRL/1, the congenic strain MRL/n, and two control strains, Balb/c and C57BL/6 mice, were fed diets which varied in the content of lipid and cholesterol. Serum cholesterol levels were highest in mice fed diets containing cholesterol and lowest in mice fed laboratory "chow." Animals fed diets that increased serum cholesterol had decreased production of prostacyclin by vascular tissue and increased production of thromboxane A2 by platelets. Prostacyclin production by heart tissue in response to arachidonic acid showed a negative correlation (r = -0.86) with serum cholesterol. In contrast, serum thromboxane demonstrated a positive correlation (r = 0.70) with serum cholesterol. The prevalence of autoimmune vasculitis seen in MRL/lpr mice was not affected by diet. However, MRL/lpr mice fed a high-fat, cholesterol-containing diet had intimal vascular lesions containing foam cells typical of arteriosclerosis. It is suggested that diets that raise serum cholesterol may influence the nature of autoimmune-mediated vascular disease by altering the balance between thromboxane and prostacyclin.     

构建不同周龄载脂蛋白E基因敲除动脉粥样硬化模型小鼠血脂和病理学观察

背景：载脂蛋白E基因敲除小鼠形成的动脉粥样硬化病变与人类全身动脉粥样硬化好发处相近,是目前建立动脉粥样硬化理想的动物模型。 目的：研究载脂蛋白E基因敲除小鼠不同周龄动脉粥样硬化的病理进程,探讨不同饮食对载脂蛋白E基因敲除小鼠动脉粥样硬化发生发展的影响。 方法：将8周龄雄性载脂蛋白E基因敲除小鼠,随机分为2组,分别给予高脂饮食和普通饮食喂养8,12,16,20,24周。 结果与结论：血清学指标检测显示,不同周龄的高脂饮食组血清中总胆固醇、三酰甘油和低密度脂蛋白胆固醇水平显著高于普通饮食组(P < 0.05),呈时间依赖性。大体和冰冻切片油红O染色结果显示,高脂饮食组动脉粥样硬化管腔斑块面积显著高于普通饮食组(P < 0.05),呈时间依赖性,此时两组各周龄小鼠管腔斑块面积相比均有显著性意义(P < 0.05),小鼠在高脂饮食16周时主动脉可见明显的脂质斑块。结果表明,实验成功构建了载脂蛋白E基因敲除动脉粥样硬化模型小鼠,此模型形成脂质条纹和纤维增生病变的时间较普通饮食组更快。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

Effects of repeated Chlamydia pneumoniae inoculations on aortic lipid accumulation and inflammatory response in C57BL/6J mice

Chlamydia pneumoniae is a common respiratory tract pathogen, and persistent infections have been associated with atherosclerosis. We studied the effects of repeated chlamydial inoculations on the inflammatory response and on aortic lipid accumulation in C57BL/6J mice. Mice fed a diet supplemented with 0.2% cholesterol were infected three or six times with C. pneumoniae every fourth week. Sera and lungs were analyzed for inflammatory responses, lung tissues were tested for the presence of C. pneumoniae DNA and RNA, and intimal lipid accumulation in the aortic sinus was quantified. High levels of chlamydial heat shock protein 60 (Hsp60) immunoglobulin G2c subclass antibodies were detected in all of the infected mice, and a positive and statistically significant correlation was found between these antibodies and autoantibodies against mouse Hsp60. Both Hsp60 antibody levels correlated with the severity of lung tissue inflammation. The cholesterol supplement in the diet had no effect on serum cholesterol levels. Significantly larger intimal lipid lesions were seen in the mouse group infected six times (6,542 mum(2)) than in the control group (1,376 mum(2); P = 0.034). In conclusion, repeated inoculations increased aortic sinus lipid accumulation in normocholesterolemic mice. The correlation between the antibodies to mouse and chlamydial Hsp60 proteins and their association with lung inflammation further support the theory of the development of an autoimmune response against heat shock proteins after repeated chlamydial infections.     

Histologic, hematologic, and biochemical characteristics of apo E-deficient mice: effects of dietary cholesterol and phytosterols

In this study, we examined the effects of a "Western-type" diet containing 9% (w/w) fat and 0.15% (w/w) cholesterol, in the presence or absence of 2% (w/w) phytosterol mixture over an 18-week period in apolipoprotein E-deficient mice. Addition of phytosterols to the high cholesterol diet was associated with normalization of the depressed hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity (from 22.3+/-6.3 to 55.4+/-19.9 pmol/mg protein/minutes, p < 0.05). This finding was associated with a significant decrease in plasma and hepatic cholesterol concentrations compared with animals fed the high cholesterol diet without phytosterols (33.3+/-5.0 versus 19.2+/-6.2 pmol/mg protein, p < 0.05). The activities of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase were comparable between the two groups of mice. Urinalyses and hematologic data were comparable between the two groups except for significantly lower platelet counts in the phytosterol-treated animals (681.6+/-118.9 versus 857.1+/-185.4 x10(9)/L, p < 0.05). The phytosterol-treated animals had significantly (p < 0.05) less fragile erythrocytes when exposed to 0.08, 0.07, or 0.05 M NaCl compared with cholesterol-fed mice. The consumption of the Western-type diet was associated with the development of xanthomatous skin lesions in 33% of the cholesterol-fed animals, but in none of the phytosterol-treated animals. Histologic examination revealed oil red O-negative vacuolation in liver and kidney parenchymal cells of the cholesterol-fed group, but not in the phytosterol-treated mice. Arrested spermatogenesis and atrophy of seminiferous tubules were observed, to a variable extent, in both groups of animals. We conclude that addition of the phytosterol mixture (2% w/w) to a Western-type diet in apolipoprotein E-deficient mice significantly decreases plasma and hepatic cholesterol concentrations, increases hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, and prevents cutaneous xanthomatosis and vacuolation in the parenchymal cells of kidneys and livers.     

Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. We have investigated the effects of graded dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Rabbits (n = 40) were fed a 0.25-1% cholesterol diet deficient in copper. Animals received either 0, 1, 3 or 20 mg copper/day and were killed after 13 weeks. Plasma cholesterol levels were similar in each dietary group. Aortic concentrations of copper were higher in the 20 mg copper/day animals compared to those receiving 0 mg copper/day (3.70 +/- 0.78 vs. 1.33 +/- 0.46 microg/g wet tissue; P < 0.05). Aortic superoxide dismutase activity was higher in animals receiving 20 mg copper/day (323 +/- 21 IU/mg tissue) compared to the other groups (187 +/- 21; 239 +/- 53; 201 +/- 33 IU/mg tissue) (P > 0.05). En face staining of aortae with oil red O showed that both high copper supplementation (20 mg/day) (67.1 +/- 5.5%) and a deficient diet (0 mg/day) (63.1 +/- 4.8%) was associated with significantly larger lesions (P < 0.05) compared to moderately supplemented animals (1 mg/day and 3 mg/day) (51.3 +/- 6.3 and 42.8 +/- 7.9%). These data indicate that in the cholesterol-fed rabbit, there is an optimal dietary copper intake and that dietary copper deficiency or excess are associated with an increased susceptibility to aortic atherosclerosis. Many Western diets contain insufficient copper and these findings indicate that a moderate dietary copper content may confer a degree of cardiac protection to the human population.     

Dietary wheaten bran in baboons: long-term effect on the morphology of the digestive tract and aorta,and on tissue mineral concentrations.

Two groups of 13 young baboons, each consisting of 8 males and 8 females, were fed on either high- or low-bran diets (based on wheat of either high or low extraction rate) for a period of 26 months. All animals grew well and remained in good condition throughout. Male (but not female) baboons on the high-bran diet had lower (p less than 0.05) concentrations of zinc in serum and bone, despite a low phytate: zinc molar ratio and a high intake of zinc. Particle-induced X-ray emission analysis showed there to be lower concentrations of calcium, copper, zinc, sulphur, potassium and nickel in the livers of baboons on the high-bran diet (P less than 0.005). Baboons on the low-bran diet passed smaller quantities of softer faeces, they had fewer nodules of lymphoid tissue in the distal portion of the colon (P less than 0.05), and within mucosal microherniations of their ileo-caecal valves the epithelial cells showed a greater tendency to squamous transformation (P less than 0.05). Mucosal microherniations of the ileo-caecal valves tended to be more frequent and larger in size (P less than 0.05) in animals of the low-bran group. Morphometrical studies did not reveal any differences in the general structural development of the digestive tract. The high-bran diet had no effect on serum cholesterol concentrations, nor on the incidence or severity of atherosclerotic lesions of the aorta.     

Dietary wheaten bran in baboons: long-term effect on the morphology of the digestive tract and aorta, and on tissue mineral concentrations

Two groups of 13 young baboons, each consisting of 8 males and 8 females, were fed on either high- or low-bran diets (based on wheat of either high or low extraction rate) for a period of 26 months. All animals grew well and remained in good condition throughout. Male (but not female) baboons on the high-bran diet had lower (p less than 0.05) concentrations of zinc in serum and bone, despite a low phytate: zinc molar ratio and a high intake of zinc. Particle-induced X-ray emission analysis showed there to be lower concentrations of calcium, copper, zinc, sulphur, potassium and nickel in the livers of baboons on the high-bran diet (P less than 0.005). Baboons on the low-bran diet passed smaller quantities of softer faeces, they had fewer nodules of lymphoid tissue in the distal portion of the colon (P less than 0.05), and within mucosal microherniations of their ileo-caecal valves the epithelial cells showed a greater tendency to squamous transformation (P less than 0.05). Mucosal microherniations of the ileo-caecal valves tended to be more frequent and larger in size (P less than 0.05) in animals of the low-bran group. Morphometrical studies did not reveal any differences in the general structural development of the digestive tract. The high-bran diet had no effect on serum cholesterol concentrations, nor on the incidence or severity of atherosclerotic lesions of the aorta.     

三磷酸腺苷结合盒转运体A1对糖尿病地鼠巨噬细胞内胆固醇外流的影响

目的探讨糖尿病地鼠巨噬细胞内胆固醇外流的改变,尤其是三磷酸腺苷结合盒转运体A1(ABCA1)的功能变化以及与载脂蛋白AI(apoA-I)的相互作用。方法用金黄地鼠高脂及糖尿病模型,分离纯化腹腔巨噬细胞,用外源性apoA-I及8-br-cAMP在体外干预巨噬细胞,测定干预前后巨噬细胞ABCA1表达和细胞内胆固醇含量的变化。结果细胞内胆固醇含量在糖尿病组高于高脂组和正常对照组。apoA-I和8-br-cAMP在体外均增加糖尿病组巨噬细胞ABCA1 mRNA的表达。apoA-I使各组细胞内胆固醇外流均增加,且与孵育时间成正比,胆固醇外流量糖尿病组高于高脂组和正常对照组。结论糖尿病鼠巨噬细胞内胆固醇大量沉积,可能与内源性apoA-I量和功能的改变所引起的ABCA1介导的细胞内胆固醇外流受阻有关。     

Experimental atherosclerosis in rabbits fed cholesterol-free diets. 5. Comparison of peanut, corn, butter, and coconut oils.

Four groups of Dutch belted rabbits were fed a semipurified diet containing 40% sucrose, 25% casein, and 14% fat for 10 months (without added cholesterol). The fats were peanut oil (PNO), corn oil (CO), butter oil (BO), and coconut oil (CNO). All diets were hyperlipidemic and hyperlipoproteinemic. The highest serum cholesterol and triglyceride levels were observed in the CNO groups, 330 and 286 mgm/dl, respectively. Serum cholesterol and triglyceride levels in the other groups (mgm/dl) were: PNO-205 and 51; CO-152 and 28; BO-292 and 48. The serum of $\text{α}\text{β}$ lipoprotein cholesterol ratios were: PNO-0.28; CO-0.28; BO-0.19, and CNO-0.13. This ratio is about 0.35–0.40 in normal Dutch belted rabbits. Liver cholesterol levels were similar in all groups (1.35 ± 0.5 gm/100 gm). Liver triglyceride levels were (gm/100 gm): PNO-0.37; CO-0.55; BO-0.66; CNO-0.39. The most severe gross atherosclerosis was observed in the CNO group (25% of surface area) and the least in the CO group (2%). The involved surface area in the other two groups was: PNO-10% and BO-14%. Microscopic evaluation of the severity of the aortic lesions indicated that the rabbits fed CNO, BO, and PNO had the most frequent and severe lesions. In contrast, the animals fed CO consistently showed much less aortic disease. Gross aortic examination revealed distinct differences in the characteristics of atherosclerotic lesions induced by the four dietary fats. The most extensive lesions, observed in rabbits fed CNO, were characterized by intimal proliferation spread over the area of lipid deposition. BO tended to produce aortic lesions rich in lipid but a relatively small number of cells and little collagen deposition. The aortic lesions in rabbits fed PNO contained relatively little lipid and were characterized by thick fibrous plaques due to prominent intimal proliferation and a high proportion of collagen. The rabbits fed CO developed few aortic lesions, with minimal intimal proliferation and very little lipid. The relative atherogenicity of PNO was an unexpected finding.     

Psychosocial stress, dietary calcium and hypertension in the spontaneously hypertensive rat

The interactive effects of psychosocial stress and diet on the development of hypertension were investigated in spontaneously hypertensive rats. Psychosocial stress, produced through manipulation of group housing conditions, was evaluated at three levels of dietary calcium and sodium: Low (0.1% Ca2+, 0.25% Na+), Intermediate (1.0% Ca2+, 0.45% Na+), and High (2.0% Ca2+, 1.0% Na+). After 13 weeks of exposure, stressed animals had higher blood pressure and lower serum ionized calcium than nonstressed animals across all diets. Likewise, animals on the low diet had higher blood pressures and lower ionized calcium values than animals on normal or high diets regardless of stress condition. The combination of stress and low diet produced the highest blood pressure and lowest serum ionized calcium values. The results suggest that stress both independently and in combination with dietary Ca2+ altered calcium metabolism. The interaction between psychosocial stress and dietary factors appears to contribute to reductions in serum ionized calcium and elevations in blood pressure in this experimental model of genetic hypertension.