高脂血症大鼠心脏、主动脉和肝脏组织中HSPA12B的表达

目的观察高脂饲料喂养的大鼠心脏、主动脉和肝脏组织中热休克蛋白A12B(HSPA12B)的表达。方法模型组和对照组SD大鼠分别经高脂饲料和普通饲料喂养16周后,测定血清总胆固醇(TC)及三酰甘油(TG);病理学观察心脏、主动脉和肝脏;用RT-PCR检测心脏、主动脉和肝脏中HSPA12BmRNA水平,用免疫组织化学法检测其蛋白表达。结果模型组总胆固醇和三酰甘油分别达(15.46±4.66)mmol/L、(0.69±0.20)mmol/L,较对照组明显升高(P<0.05);病理学观察发现模型组形成高脂性心脏病变及肝脏脂肪变性;模型组心脏、主动脉和肝脏组织中HSPA12BmRNA的表达显著高于对照组(P<0.01);模型组HSPA12B呈较强阳性表达(P<0.05)。结论高脂饲料喂养能使大鼠形成高脂血症,并引起心脏、主动脉和肝脏中HSPA12B的表达升高。     

Cigarette smoke-induced depression in LCAT activity

The effect of acute inhalation of cigarette smoke on plasma cholesterol esterification by lecithin-cholesterol acyltransferase (LCAT) in atherosclerosis-susceptible White Carneau pigeons was examined. Pigeons were assigned to four treatment groups: (1) Shelf Control fed a chow diet and not exposed to smoke products; (2) Sham pigeons fed a cholesterol-saturated fat diet and exposed to fresh air by the Lorillard smoking machine; (3) low nicotine-low carbon monoxide (LoLo) animals also fed the cholesterol diet and exposed to low concentrations of these cigarette smoke products; and (4) high nicotine-high carbon monoxide (HiHi) birds fed the cholesterol diet and subjected to high concentrations of these inhalants. Both Control and Sham birds had significantly higher LCAT activity (percentage esterification per minute) than HiHi pigeons. Experiments designed to determine whether altered enzyme and/or substrate were responsible for depressed activity revealed no smoke-related modification in substrate efficiency. In addition, Sham and HiHi pigeons had similar concentrations of plasma-free cholesterol, high density lipoprotein (HDL) cholesterol, cholesteryl ester and phospholipid, and similar HDL phospholipid and cholesteryl ester fatty acid profiles. However, reduced LCAT activity in HiHi pigeons can be explained by (1) impairment of enzyme efficiency as estimated by in vitro analysis; and (2) in vivo reduction in levels of LCAT cofactor, HDL apoprotein A-I.     

Development of atherosclerosis in Balb/c apolipoprotein E-deficient mice

BACKGROUND: Since its creation in 1992 by gene inactivation via gene targeting, the apolipoprotein E "knockout" mouse has become the most widely used rodent model for the study of atherosclerosis. Commercially available apolipoprotein E(-/-) mice are bred on a C57BL/6J background. The goal of the present study was to investigate the development of atherosclerosis in apolipoprotein E-deficient mice generated on a Balb/c background. METHODS: We compared serum cholesterol concentrations and the development of atherosclerotic lesions in heterozygous Balb/c [apolipoprotein E(+/-)] mice fed regular rodent chow, Balb/c apolipoprotein E-deficient mice fed regular chow, and Balb/c apolipoprotein E-deficient mice fed a high-fat diet for up to 30 weeks. Expression of the chemokine JE (murine homologue of MCP-1), as well as the adhesion molecules E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, in the aortas of knockout mice fed a high-fat diet was measured by enzyme-linked immunosorbent assay. RESULTS: Balb/c apolipoprotein E-deficient mice develop atherosclerotic lesions in a reproducible temporal and morphological pattern. Total serum cholesterol concentrations in Balb/c apolipoprotein E-deficient mice fed regular chow or a high-fat diet, respectively, closely parallel those reported for C57BL/6J apolipoprotein E-deficient mice. The expression of all three adhesion molecules in the aorta follows a similar temporal pattern, peaking in the first 15 weeks, whereas JE concentrations peak around 23 weeks. CONCLUSION: The availability of Balb/c apolipoprotein E-deficient mice will facilitate the study of atherosclerosis in a mouse strain that can concomitantly develop other pathological states that are not readily inducible in mice with the C57BL/6J background.     

Antioxidant and anti-atherogenic activities of three Piper species on atherogenic diet fed hamsters

Atherogenic diet is known to induce high plasma lipid concentration, oxidative stress and early atherosclerosis. Antioxidants have potentials to counter the effect of atherogenic diet.The present research aims at evaluating the antioxidant and anti-atherosclerotic activities of three Piper species (Piper guineense, Piper nigrum and Piper umbellatum) on atherogenic diet fed hamsters.Hamsters divided into 8 groups: normal control, atherosclerotic control and six test groups. The normal animals fed normal rodent chow, the atherosclerotic control animals fed the same rodent chow supplemented with 0.2% cholesterol and 10% coconut oil (high cholesterol diet). The 6 test groups’ animals fed same diet as the atherosclerotic control group but with additional supplementation of 2 graded doses (1 and 0.25 mg/kg body weight, o.p.) of plant extracts for 12 weeks.The atherogenic diet induced a collapse of the erythrocyte antioxidant defense system (significant decrease in superoxide dismutase, catalase and glutathione peroxidase activities). Atherogenic diet also induced an increase in plasma total cholesterol, triglyceride, thiobarbituric acid reactive substances (TBARS), oxidation of low density lipoprotein cholesterol (LDL) and accumulation of foam cells in the aorta a hall mark for atherosclerosis. Administration of the Piper species prevented the collapse of the antioxidant system and the increase of plasma parameters maintaining them towards normality. The Piper species also prevented LDL oxidation by increasing the time (lag time) for its oxidation.The results suggest that these Piper species have significant antioxidant and anti-atherogenic effect against atherogenic diet intoxication.     

Late effects of early feeding of a low cholesterol diet on the intestinal active and passive transport properties in the rabbit

It has previously been demonstrated that a short period of feeding of a low cholesterol diet (LCD) alters the active and passive transport properties of the intestine. This study was undertaken to determine the late effect of early nutrition with LCD. An in vitro technique was used to determine the uptake of glucose, galactose, leucine, medium- and long-chain fatty acids, cholesterol and bile acids into the jejunum, ileum and colon of rabbits. Five dietary groups were used: group A was fed chow for 16 weeks; group B was fed chow for 14 weeks followed by LCD for 2 weeks; group C was fed chow for 2 weeks, LCD for 2 weeks, chow for 10 weeks, and LCD for 2 weeks; group D was fed chow for 2 weeks and LCD for 14 weeks; and group E was fed chow for 2 weeks, LCD for 2 weeks and chow for 14 weeks. Animals fed LCD for 2 weeks at an early age demonstrated different alterations in the active and passive transport of these solutes as compared with animals exposed to LCD for only 2 weeks at a later age (group C vs. group D). Feeding the animals chow for 12 weeks after 2 weeks of LCD (group E) did not result in a normalization of the altered intestinal transport. The transport changes were progressive, with qualitative and quantitative differences in animals fed LCD for 2 weeks (group B) as compared with animals fed LCD for 14 weeks (group D). These changes in intestinal transport were not due to differences in food consumption or mucosal weight but were likely of nutritional significance, since the animals' body weight gain differed in animals fed chow as compared with those fed LCD. Thus, (1) feeding LCD is associated with alterations in the active and passive jejunal, ileal and colonic uptake of nutrients; (2) these alterations are influenced by the duration of feeding LCD; (3) the effects of LCD persist for at least 10 weeks after the diet is stopped and feeding with chow is restored; and (4) rechallenge with LCD following an earlier exposure to LCD is associated with an accentuation of the intestinal effects of LCD. It is concluded that these late effects of early nutrition with a low cholesterol diet upon intestinal transport function may have an important impact on the nutritional status of the animal.     

Effects of soybean phospholipid,chlorella phospholipid,and clofibrate on collagen and elastin synthesis in the aorta and on the serum and liver lipid contents in rats

The effects of antilipemic agents, soybean polyunsaturated phospholipid (SP), clofibrate, and chlorella phospholipid (CP), on the serum and liver lipid contents and on the synthesis of collagen and elastin in the thoracic aorta in rats were investigated. SP (1%), CP (1%), and clofibrate (0.1%) were added to the basal diet, and the diets were given for 5 weeks to rats from 10 to 15 weeks old. Serum cholesterol and phospholipid contents and liver cholesterol and triglyceride contents were significantly decreased in rats fed CP and clofibrate containing diet compared to the control animals. The contents of collagen and elastin in the thoracic aorta were not changed by CP or clofibrate, although in rats fed the SP-containing diet, incorporation of hydroxyproline from proline into elastin increased. However, the prolin hydroxylase activity in the thoracic aorta was significantly increased (twofold) in CP and clofibrate rats compared to the control and SP animals. In spite of the fact that clofibrate and CP activate the proline hydroxylase activity in the aorta, collagen and elastin content and the incorporation of proline as hydroxyproline into collagen and elastin in the aorta did not increase.     

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.     

高脂高胆固醇饮食对3基因突变小鼠动脉粥样硬化性病变的影响

目的： 探讨高脂高胆固醇饮食性因素对3个脂代谢相关基因突变小鼠血脂代谢及动脉内膜损伤的影响。方法：分析高脂高胆固醇饮食喂养的3基因突变（ApoE-/-/LDLR-/-/Leprdb/db）小鼠血脂、血糖水平和主动脉内膜病变的特点。结果：高脂高胆固醇饮食喂养的3基因突变小鼠血浆总胆固醇（TC）、甘油三酯（TG）和血糖水平均显著高于普通饮食组。该饮食喂养2周和5周龄小鼠血浆TC、TG的浓度分别达(106.75±3.40) mmol/L和(9.12±1.35) mmol/L,高出普通饮食组4.33和2.36倍。主动脉内膜出现灶状内皮肿胀、脱落、单核/淋巴细胞黏附以及泡沫细胞形成。随喂养周数的增加出现内弹力板排列不整、部分断裂、内皮和平滑肌细胞内脂质沉积,并发生内膜增生型病变增多、范围扩大。血脂紊乱的加重与动脉内膜的损伤呈正相关。高脂高胆固醇饮食组小鼠的血脂紊乱和动脉内膜损伤均较普通饮食组严重,并伴有明显的肝细胞脂肪病变。结论：高脂高胆固醇饮食促进了3基因突变小鼠血脂代谢紊乱及主动脉内膜损伤的发生,提前并加重了动脉粥样硬化性病变的发生发展。     

脂肪分化相关蛋白反义寡核苷酸抑制细胞内胆固醇积聚及其在动脉粥样硬化中的改变

目的：研究ADRP与As发生和发展的关系。方法： 使用80 mg/L Ox-LDL和/或1 mmol/L反义ADRP寡核苷酸与小鼠腹腔巨噬细胞共孵育72 h。测定细胞内胆固醇酯；油红O染色显示细胞内中性脂质；RT-PCR和Western blotting观察反义寡核苷酸对ADRP表达的影响。高胆固醇饲料喂养新西兰白兔12周，复制As模型。测定血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯及动脉壁胆固醇；苏丹Ⅳ染色显示主动脉病变面积；HE染色观察主动脉及肝脏的病变；免疫组织化学方法显示ADRP在主动脉病变区及肝脏中的表达。 结果： 反义ADRP寡核苷酸使细胞内胆固醇酯由（46.6±3.4）mg/g protein下降到（19.9±1.9）mg/g protein，细胞内中性脂质明显减少，ADRP基因和蛋白的表达显著下降。喂高胆固醇饲料的动物血清TC、LDL-C、TG及动脉壁胆固醇显著升高，主动脉病变面积为（40.1±7.3）%，ADRP在主动脉病变区免疫组织化学染色强阳性，在肝脏中染色阴性。结论： 反义ADRP寡核苷酸能够明显抑制由氧化低密度脂蛋白引起的小鼠腹腔巨噬细胞中胆固醇酯的聚集。ADRP在兔As病变中表达明显增高。提示高表达ADRP促使As发生和发展。     

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.     

Experimental cholelithiasis in the ground squirrel

Richardson's ground squirrels of both sexes were fed a 2% cholesterol-enriched rat chow diet for various intervals from 6 hours through 20 weeks. Bile was withdrawn from the organs and analyzed biochemically to obtain a lithogenic index. The remaining luminal contents were rinsed from the resected organs and examined by light and scanning electron microscopy. Gallbladder tissue was fixed and examined in a similar fashion to observe the luminal aspect of the epithelial sheet. Scanning electron microscopy revealed increased mucus secretion before precipitation of rhomboidal cholesterol monohydrate crystals from the lithogenic bile. The crystals grew by appositional layering into microliths and then by aggregation into mulberry-shaped stones. Mucus hypersecretion continued to be a common epithelial observation throughout the study. Five days after introduction of the diet, a thick discontinuous sludge-like layer was observed overlying large regions of the epithelial sheet. In later stages, this material was observed embedding cholesterol crystals into the surface aspect of the stone. By 20 weeks many stones were approximately 2 mm in diameter and were accompanied by large numbers of various sized concrements. The nature of the cholesterol crystals and stone formation pattern closely resembled that reported for humans. The ground squirrel fulfills all criteria required to be regarded as an excellent animal model and is well suited for continued study into the role of the epithelial cell during cholesterol cholelithiasis.     

Effects of chlorella phospholipid on the aortic collagen and elastin metabolism and on the serum lipid content in rats with experimental arteriosclerosis

Rats treated with 44,800 IU of vitamin D₂ for 4 consecutive days were fed an atherogenic diet in the presence or absence of 1% chlorella phospholipid. Control rats received a basal diet and were administered olive oil. After 2 months the animals were killed and aortic prolyl hydroxylase, lysyl oxidase activity, collagen, elastin, and serum lipid levels were determined. Aortic prolyl hydroxylase activity was significantly decreased in rats receiving the atherogenic diet in the absence of chlorella phospholipid. The aortic collagen and elastin content was lower in rats additionally treated with chlorella phospholipid. Aortic lysyl oxidase activity was significantly decreased in all rats receiving the atherogenic diet. The serum cholesterol level was significantly higher in rats on the atherogenic diet, especially the absence of chlorella phospholipid supplementation. The findings suggest that the administration of chlorella phospholipid may stimulate the degradation of collagen and elastin in the aorta of rats fed an atherogenic diet and that the serum cholesterol lowering effect of chlorella phospholipid is not ascribable to thyroid functions. Furthermore, the results suggest that the aortic degradation rate of elastin was reduced by the atherogenic treatment.     

Rapid increase of glycosaminoglycans in the aorta of hypercholesterolemic rats; a negative correlation with plasma HDL concentration.

Rats were kept either on a standard laboratory diet or a high cholesterol, olive oil diet for periods ranging from 1 day to 22 weeks. The effect of the high cholesterol, olive oil diet on the concentrations of cholesterol, glycosaminoglycans (GAGs) and collagen in aortic intima-media, were studied and the developing hyperlipidemia was characterized. The concentration of cholesterol in rat aorta was increased after 22 weeks' high cholesterol, olive oil diet, while collagen concentration was not affected. On the contrary, the concentration of aortic sulphated GAGs was significantly increased already after one week's high cholesterol, olive oil diet. The diet increased the formation of a cholesterol-rich very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL)-associated cholesterol and phospholipids, but had virtually no effect on low density lipoprotein (LDL)-lipids. The concentrations of VLDL-cholesterol and -phospholipids showed positive correlations with the concentration of aortic GAGs (r = 0.89 and 0.83, respectively, P less than 0.05 for both). Stronger (negative) correlations were found between aortic GAGs and HDL-cholesterol and -phospholipids (r = 0.94 for both, P less than 0.01) suggesting that HDL may have a role in the control of arterial sulphated GAG concentration.     

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.     

吡格列酮对高脂血症大鼠主动脉结缔组织生长因子表达水平的影响

目的:观察吡格列酮对高脂血症大鼠主动脉结缔组织生长因子(CTGF)表达的影响。方法:将26只雄性SD大鼠按体重随机分成普通饲料对照组(9只)和高脂饲料组(17只),分笼饲养,12周后检测其空腹血脂水平,以确定高脂饲料组造模成功;再将成模大鼠随机分为模型组(8只)和吡格列酮组(9只)。第13周起予吡格列酮组大鼠吡格列酮(10mg/kg/天),余两组用等量生理盐水连续灌胃4周后,平行检测各组大鼠血脂水平,主动脉组织形态学(包括光镜、电镜),免疫组化检测主动脉CTGF表达,并用Image-ProPlus图像分析系统分析染色结果。结果:高脂饲料喂养12周后,大鼠总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平较对照组明显升高(P<0.01),造模成功。吡格列酮组给药4周后血清TC、TG水平较模型组明显降低(P<0.01),主动脉CTGF表达也显著下调(P<0.01)。光镜下可见吡格列酮组内皮细胞偶有脱落,内膜下少量泡沫细胞,平滑肌细胞轻度增生;电镜下可见吡格列酮组大鼠血管内皮层整齐,偶见线粒体水肿,中膜平滑肌细胞少见泡沫样变,均较模型组好转。结论:主动脉CTGF表达增加参与了高脂血症对大鼠血管内膜的损伤,吡格列酮干预能够降低主动脉CTGF表达,减轻主动脉内膜损伤,对动脉粥样硬化有保护作用。     

猕猴脑动脉硬化造型过程中血清脂质的变化

高脂高胆固醇喂养幼年(2—4岁)和成年(10—13岁)雄性猕猴16—17个月,并辅以服用甲基琉氧嘧啶。实验结果,发现第二个月的胆固醇水平超过250mg%,并持续到实验结束。低密度脂蛋白—胆固醇(LDL—C),伴随着总胆固醇升高而升高,甘油三酯(TG)和高密度脂蛋白—胆固醇(HDL—C)变化不大。幼年和成年组之间无显著性差异。     

Rapid increase of glycosaminoglycans in the aorta of hypercholesterolemia rats; a negative correlation with plasma HDL concentration

Rats were kept either on a standard laboratory diet or a high cholesterol, olive oil diet for periods ranging from 1 day to 22 weeks. The effect of the high cholesterol, olive oil diet on the concentrations of cholesterol, glycosaminoglycans (GAGs) and collagen in aortic intima-media, were studied and the developing hyper-lipidemia was characterized. The concentration of cholesterol in rat aorta was increased after 22 weeks' high cholesterol, olive oil diet, while collagen concentration was not affected. On the contrary, the concentration of aortic sulphated GAGs was significantly increased already after one week's high cholesterol, olive oil diet. The diet increased the formation of a cholesterol-rich very low density lipoprotein (VLDL), decreased high density lipoprotein (HDL)-associated cholesterol and phospholipids, but had virtually no effect on low density lipoprotein (LDL)-lipids. The concentrations of VLDL-cholesterol and -phospholipids showed positive correlations with the concentration of aortic GAGs (r = 0.89 and 0.83, respectively, P < 0.05 for both). Stronger (negative) correlations were found between aortic GAGs and HDL-cholesterol and -phospholipids (r = -0.94 for both, P <0.01) suggesting that HDL may have a role in the control of arterial sulphated GAG concentration.     

Dietary induced hyperbetalipoproteinemia in chimpanzees: comparison to the human hyperlipoproteinemia

Fasting plasma from chimpanzees fed normal and atherogenic diet was separated into alpha (HDL) and beta (LDL) lipoproteins by electrochromatography. Both lipoproteins were analyzed for lipid and fatty acid composition.Beta lipoproteins, esterified cholesterol, free cholesterol, and phospholipids were increased in chimpanzees fed the atherogenic diet. The cholesterol/phospholipid ratio was increased. These lipid changes occurred chiefly in the beta lipoproteins. A disproportionate increase of plasma phosphatidylcholine to sphingomyelin was confirmed. Differences in the fatty acid composition of both lipoproteins were noted and cholesterol oleate was elevated more than cholesterol linoleate so that the $\text{18:1}\text{18:2}$ ratio was increased. The intima of one animal which died from myocardial infarction after 4–5 years diet showed an increase of cholesterol oleate.Similarities between cholesterol-induced lipoprotein changes in chimpanzees and those obtained in human hyperbetalipoproteinemia are discussed. These similarities stress the usefulness of these nonhuman primates as a model for experimental atherosclerosis and for studying the molecular changes in lipoprotein patterns.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.