低密度脂蛋白胆固醇升高在家兔动脉粥样硬化发生发展中的意义

目的观察低密度脂蛋白胆固醇(LDL-c)对家兔动脉粥样硬化(AS)形成的影响,探讨AS的发生机制。方法以高脂饲料复制家兔实验性AS模型,分阶段检测家兔血清胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-c)和低密度脂蛋白胆固醇(LDL-c)含量;观察主动脉内膜病理学变化;分析主动脉内膜增生程度及AS斑块面积与血浆脂蛋白水平的相关性。结果高脂组家兔主动脉粥样硬化面积和内膜增生程度明显较对照组增加(P<0.01),血浆LDL-c水平明显较对照组升高(P<0.01);动脉内膜增生程度及AS斑块面积均与血浆LDL-c水平呈非常显著正相关(r=0.837,P<0.001)。结论提示血浆LDL-c水平升高,是致AS发生发展的重要原因。     

Evaluation of rat and rabbit sera lipoproteins in experimentally induced hyperlipidemia by analytical ultracentrifugation

Animals of various species are widely used as models with which to study atherosclerosis and the lipoprotein metabolism. The objective of this study was to investigate the lipoprotein profiles in Wistar rats and New Zealand white rabbits with experimentally induced hyperlipidemia by means of ultracentrifugation. The Schlieren curves were utilized to compare suckling and adult rat sera to determine whether aging causes alterations in lipoprotein profiles. A striking feature of the data is the high concentration of low-density lipoproteins (LDL), (>5.2 mmol/l cholesterol) in the 2-week old rat serum pool which was greatly decreased in the 3-weeks rat serum pool (<1.3 mmol/l cholesterol). Additional experiments were performed to permit a direct comparison of the amounts of lipoprotein present in rat sera in experimental hyperlipidemia post-Triton WR 1339 administration. Rapid changes in concentrations in very low-density lipoproteins (VLDL), LDL and high-density lipoproteins (HDL) were observed after Triton injection. The administration of Triton WR 1339 to fasted rats resulted in an elevation of serum cholesterol levels. Triton physically alters VLDL, rendering them refractive to the action of lipolytic enzymes in the blood and tissues, preventing or delaying their removal from the blood. Whereas the VLDL concentration was increased markedly, those of LDL and HDL were decreased at 20 h after Triton treatment. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate of LDL aliquots, to prepare radioactive-labeled lipoproteins and to study induced hyperlipidemia in rabbits. Analytical ultracentrifugation was applied to investigate the LDL flotation peaks before and after cholesterol feeding of rabbits. Modified forms of LDL were detected in the plasma of rabbits with experimentally induced atherosclerosis. ApoB-containing particles, migrating as LDL, intermediate density lipoproteins and VLDL were the most abundant lipoproteins. Gamma camera in vivo scintigraphy on rabbits with radiolabeled lipoproteins revealed visible signals corresponding to atherosclerotic plaques of the aorta and carotid arteries.     

APA hamster model for diabetic atherosclerosis. 2. Analysis of lipids and lipoproteins.

Syrian hamsters of the APA strain (APA hamsters) have recently been shown to have atheromatous lesions in the aortic arches under diabetic condition induced by a single injection of streptozotocin (SZ). In that model, fatty streaks, which are the initial lesions of atherogenesis, develop by 6 weeks after the injection (WAI). In this study, we evaluated plasma lipid concentrations and lipoprotein profiles in diabetic APA hamsters at 6 WAI to reveal the early stage of atherogenesis clinicopathologically. As a result, by biochemical analysis, hyperglycemic APA hamsters showed signs of hypercholesterolemia and hypertriglyceridemia. Low-density lipoprotein (LDL) cholesterol significantly increased, but high-density lipoprotein (HDL) cholesterol significantly decreased. Agarose gel electrophoresis showed an obvious increase in the fractions of chylomicron, LDL and abnormal lipoprotein. Plasma LDL in diabetic animals was in a state more susceptible to oxidization. In addition, a significant increase in glycated LDL was also found in the diabetic animals by enzyme linked immunosorbent assay (ELISA). Moreover, lipid peroxidation product (4-hydroxynonenal (4 HNE))-adducted proteins and advanced glycation end-products (AGE) were immunohistochemically detected in the foam cells of the fatty streaks. These results revealed that diabetic APA hamsters had hyperlipidemia characterized by increases in chylomicron, LDL and abnormal lipoprotein, and suggested that oxidized LDL and/or glycated LDL might be actively uptaken by macrophages and play an important role in the initial stage of atherogenesis.     

Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.     

Transient experimental anemia in cholesterol-fed rabbits induces systemic overexpression of the reticulocyte-type 15-lipoxygenase and protects from aortic lipid deposition

Oxidative modification of low-density lipoprotein has been implicated in atherogenesis and the lipid peroxidizing enzyme 12/15-lipoxygenase (12/15-LOX) was suggested to be involved. For this study, we induced a strong and long-lasting systemic overexpression of the 15-LOX, in female New Zealand White rabbits by transient experimental anemia. After the hematopoietic parameters had returned to normal, these animals and age-matched controls were fed a lipid-rich Western-type diet for 10 weeks. Analyzing the lipid deposition in the aortic wall, we found that the 15-LOX overexpressing rabbits deposited significantly (P<0.01) less cholesteryl linoleate in the thoracic aorta than the corresponding controls. Similar results were obtained when free cholesterol and cholesteryl oleate were quantified. However, in the aortic arch where lipid deposition was much more severe a similar trend was observed, but the effects were not significant any more. Comparative determination (lipoxygenase overexpressing vs. control animals) of various plasma parameters as well as histological inspections of major organs did not reveal any indications for major organ malfunction. These data suggest that transient experimental anemia, which is accompanied by a long-lasting overexpression of the reticulocyte-type 15-LOX protects cholesterol-fed rabbits from lipid deposition in the aortic wall.     

Urotensin II Promotes Atherosclerosis in Cholesterol-Fed Rabbits

Urotensin II (UII) is a vasoactive peptide composed of 11 amino acids that has been implicated to contribute to the development of cardiovascular disease. The purpose of this study was to investigate whether UII affects the development of atherosclerosis in cholesterol-fed rabbits. UII was infused for 16 weeks through an osmotic mini-pump into male Japanese White rabbits fed on a high-cholesterol diet. Plasma lipids and body weight were measured every 4 weeks. Aortic atherosclerotic lesions along with cellular components, collagen fibers, matrix metalloproteinase-1 and -9 were examined. Moreover, vulnerability index of atherosclerotic plaques was evaluated. UII infusion significantly increased atherosclerotic lesions within the entire aorta by 21% over the control (P = 0.013). Atherosclerotic lesions were increased by 24% in the aortic arch (P = 0.005), 11% in the thoracic aorta (P = 0.054) and 18% in the abdominal aorta (P = 0.035). These increases occurred without changes in plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or body weight. Immunohistochemical staining revealed that macrophages and matrix metalloproteinase-9 were significantly enhanced by 2.2-fold and 1.6-fold in UII group. In vitro studies demonstrated that UII up-regulated the expression of vascular cell adhesion protein-1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells, which was inhibited by the UII receptor antagonist urantide. In conclusion, our results showed that UII promotes the development of atherosclerotic lesions and destabilizes atherosclerotic plaques in cholesterol-fed rabbits.     

Role of lipolytic enzymes in the development of hyperlipidemia induced by administration of heterologous albumin in rabbits

Experiments on rabbits have shown hyperlipidemia to develop within the first 48 h after a single intravenous injection of bovine serum albumin (BSA, fraction V). The mean concentration of blood plasma triglycerides (TG) was considerably higher than normal (by 262% after 24 and by 625% after 48 h). The cholesterol content was also elevated (by 80 and 270%, respectively). Following 7 and 14 days the lipid concentration returned to normal. The plasma post-heparin lipoprotein lipase activity (PHP-LPL) was lower 24 h and 7 days after BSA injection and the hypotriglyceridemic effect of heparin was less pronounced. The data obtained support the hypothesis that hyperlipidemia provoked by a single intravenous injection of BSA to rabbits results from low PHP-LPL activity and possible changes in TG-rich lipoprotein substrate affinity for the enzyme.     

Adipophilin在动脉粥样硬化病变和脂质负荷细胞中的作用研究(英文)

Adipophilin是细胞内脂质聚集和与脂质聚集有关疾病的标志物 ,巨噬细胞源性泡沫细胞的形成是动脉粥样硬化性疾病发生的重要环节 .为了探讨adipophilin在动脉粥样硬化性疾病的作用 ,通过高胆固醇饲料喂养新西兰白兔 12周 ,复制动脉粥样硬化疾病模型 ,同时测定血脂的变化和动脉壁胆固醇 ,使用HE染色、苏丹Ⅳ染色观察动脉粥样硬化病变的形成 ,使用免疫组织化学的方法观察动脉粥样硬化病变处和动物肝脏中adipophilin的表达 .结果发现 ,高胆固醇饲料喂养组血清总胆固醇、低密度脂蛋白胆固醇和动脉壁胆固醇明显增高 ,动脉粥样硬化病变面积增加到 (40 0 6± 7 2 9) % ,动脉粥样硬化病变处adipophilin表达呈阳性 ;而adipophilin在肝脏中的表达无论是高胆固醇饲料喂养组或对照组均为阴性 .使用80mg/L OxLDL与小鼠腹膜巨噬细胞共孵育 ,复制脂质负荷细胞 ,然后把构建的 1mmol/Ladipophilin反义寡核苷酸与该细胞共孵育 .结果发现 ,使用油红O染色观察的细胞内脂滴明显减少 ,生化测定细胞内胆固醇酯显著降低 ,与对照组相比 ,差别有显著性 .说明adipophilin与动脉粥样硬化病变有密切的关系 ,控制adipophilin的表达能够减少巨噬细胞细胞内胆固醇酯的聚集     

A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits

A new and convenient animal model for studying peripheral vascular and coronary artery disease in diabetes was established in this study. Male New Zealand White rabbits weighing approximately 2 kg were divided into 2 groups: a normal control group fed standard laboratory chow and a diabetogenic diet–fed group received a high-fat/high-sucrose diet. The high-fat/high-sucrose diet (contained 10% lard and 37% sucrose) feeding was maintained for 6 months. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, superoxide dismutase, nitric oxide, nitric oxide synthase, insulin, and glucose were quantitated at monthly or bimonthly intervals. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. The aortic samples were observed by electron microscopy. High plasma triglyceride and glucose concentrations were induced. At the end of 6 months, the aortic fatty streak lesions were present in the animals'' vascular specimens. As far as we know, this is the first report that demonstrates that New Zealand White rabbits can develop obvious aortic fatty streaks by feeding a high-fat/high-sucrose diet. Our results suggest that NewZealand White rabbits fed a high-fat/high-sucrose diet would provide a convenient model for studying peripheral vascular and coronary artery disease in diabetes.     

Testosterone & lipid metabolism in rabbits.

Testosterone and lipid metabolism was studied in rabbits. The effect of orchidectomy in rabbits fed normal diets and of testosterone propionate administration to these animals on total cholesterol, phospholipids, and triglycerides of serum, liver, aortic arch, thoracic aorta, and abdominal aorta as well as the activity of lipoprotein lipase in the aortic segments and heart was investigated. With a few exceptions, total cholesterol,phospholipids, and triglycerides increased in these tissues in orchidectomized animals and testosterone counteracted this increase. 3 segments of the aorta revealed variations in response to lipids in the orchidectomized animals as well as in the testosterone administered. Lipoprotein lipase activity decreased in the heart and the 3 aortic segments on orchidectomy, and testosterone administration caused increased enzyme activity.     

Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits

The hypothesis was tested that resveratrol, a compound in red wine, would inhibit atherosclerotic development in rabbits fed 0.5% cholesterol for 60 days. Rabbits were supplemented with or without oral resveratrol. During the study, body weights and food consumption were similar for the two groups. The lack of differences between liver weights and a series of serum parameters indicative of liver disease suggest that liver function was similar in the two groups. The diet produced hypercholesterolemia in both groups, but no differences in lipoprotein-cholesterol concentrations. The electrophoretic mobility of plasma low-density lipoprotein (LDL) and plasma LDL after induced oxidation also was not different between the groups. Staining of atherosclerotic lesions in the control and resveratrol-treated groups revealed that the resveratrol-treated rabbits had significantly more aortic surface area covered by atherosclerotic lesions (P < 0.02). Therefore, resveratrol promoted atherosclerotic development, rather than protect against it, by a mechanism that is independent of observed differences in gross animal health, liver function, plasma cholesterol concentrations, or LDL oxidative status.     

Expression of lipoprotein receptors in the aortic walls of diabetic APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ. In semi-quantitative RT-PCR, scavenger receptor (SR)-AI, macrosialin (MS)/CD68, and receptor for advanced glycation end-products (RAGE) mRNAs showed significant increases at 6 WAI of SZ, and SR-AI and CD36 mRNA obviously increased until 26 WAI, as compared with the control. Low-density lipoprotein receptor mRNA showed a significant decrease at 14 and 26 WAI, and SR-BI mRNA significantly decreased at 6 and 14 WAI, as compared with the control. Very low-density lipoprotein receptor mRNA was at the same level as the control. By means of in situ hybridization, SR-AI, MS/CD68 and RAGE mRNA were detected in the foam cells of the fatty streaks at 6 WAI, which suggested that SR-AI, MS/CD68 and RAGE play crucial roles in the formation of the fatty streaks, the initial lesions of atherogenesis in diabetic APA hamsters. SR-AI and CD36 were also believed to be related to the progression of atherogenesis in this model.     

Receptor-mediated catabolism and tissue uptake of human low density lipoprotein in the cholesterol-fed, atherosclerotic rabbit

The LDL receptor pathway, which was delineated in cultured cells, is now known to operate in vivo. In this study we have measured the plasma clearances and tissue uptakes of native and chemically modified (1,2-cyclohexanedione-treated or reductively methylated) LDL in rabbits in order to determine the response of the pathway to a high-cholesterol diet. 1 week on the diet increased circulating LDL and suppressed its receptor-mediated plasma clearance and uptake into all tissues. The fractional catabolic rate of the lipoprotein via the receptor-independent route also fell. Continuation of the feeding program for 12 weeks accentuated these changes and virtually eliminated receptor uptake into all tissues so that the plasma decay curves of native and cyclohexanedione-treated LDL were superimposable. Lipoprotein assimilation by the aorta, however, did not follow this general trend. This tissue, after 12 weeks, was variably infiltrated by atheromatous deposits and the appearance of these lesions was associated with a substantial increase in the relative uptakes of both native and chemically modified (cyclohexanedione-treated and reductively methylated) LDL. We concluded (a) that expansion of tissue cholesterol pools virtually abolishes LDL receptor activity in rabbits; and (b) that LDL assimilation (both apparently receptor-mediated and receptor-independent) paradoxically increases at sites where the aorta is affected by atheromatous lesions.     

家兔低密度脂蛋白胆固醇增高及同步饮磁处理水时动脉内膜病理学变化的比较研究

目的:观察家兔实验性低密度脂蛋白胆固醇(LDL -c)增高及同步饮磁处理水时动脉内膜病理变化的区别,探讨磁处理水对动脉粥样硬化的预防作用。方法:新西兰雄性大白兔随机分为3组即对照组(NG)、模型组(ASG)和预防组(MWG) ,以高脂饲料复制家兔动脉粥样硬化(AS)模型。MWG家兔喂高脂饲料同步饮磁处理水,分阶段检测各组家兔血浆LDL -c含量并观察其主动脉内膜病理学改变。结果:MWG血浆LDL -c含量明显较ASG降低(P <0 .0 1,MWG主动脉内膜脂质沉积及粥样斑块形成面积较ASG减小(P <0 .0 1,内膜增生程度较ASG减轻(P <0 .0 1)。结论:提示磁处理水在家兔实验性高LDL -c血症及AS的预防中起一定作用。     

Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet

The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis.     

Lipid keratopathy and atheromatosis in an SPF laboratory rabbit colony attributable to diet

Sporadic cases of corneal opacity occurred in an SPF rabbit colony fed on a diet containing 10% white fish-meal. Routine histological monitoring also revealed atheromatous lesions involving the intima of the aorta, coronary arteries and the arteries of other organs in 29 rabbits examined. Serum cholesterol levels above 10 mmol/l were found in 7 rabbits, including 4 affected with corneal lesions, which proved to be lipid keratopathy on histochemical and electron microscopical examination. The serum cholesterol level was found to be within normal range (below 2.27 mmol/l) in 10 rabbits reared entirely on a modified version of the diet, where the 10% fish-meal content was replaced with 10% grass-meal. No more ocular or atheromatous lesions have been found since the adoption of the new diet for the colony.     

Effects of probucol on atherosclerosis of apoE-deficient or LDL receptor-deficient mice.

The effect of probucol on atheroma formation was evaluated using mouse models for atherosclerosis with different diet protocols. Dietary administration of probucol (0.5 %, wt/wt) for 12 weeks reduced total plasma cholesterol levels in both apolipoprotein E (apoE)-deficient mice fed a western diet and in low-density lipoprotein receptor (LDLR)-deficient mice fed a Paigen diet by 60 % and 30 % to 60 %, respectively. Probucol treatment also significantly reduced high-density lipoprotein (HDL) levels in apoE-deficient mice, but not in LDLR-deficient mice. Atherosclerotic plaques in the aortic sinus of probucol-treated apoE-deficient mice were two-fold larger than those in untreated apoE-deficient mice, while the lesions in probucol-treated LDLR-deficient mice were similar to those in untreated LDLR-deficient mice. A strong negative correlation between HDL cholesterol levels and lesion sizes at the aortic sinus was observed in apoE-deficient mice, but not in LDLR-deficient mice. Thus, in contrast to LDLR-deficient mice, probucol had a strong proatherogenic effect in the aortic sinus of apoE-deficient mice associated with the reduction of HDL levels in spite of the reduction of total plasma cholesterol levels. The varying effects of probucol on atherogenesis depend upon the portion of aorta and which animal model is evaluated, implicating that complex cellular events are involved in the effect of probucol.     

Increase in hepatic low-density lipoprotein receptor activity during pregnancy in Watanabe heritable hyperlipidemic rabbits; an animal model for familial hypercholesterolemia

In homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, the serum cholesterol level and serum low-density lipoprotein (LDL) level decreased from 562 +/- 76 (mean +/- S.E.) to 144 +/- 34 mg/dl and 410 +/- 56 to 90 +/- 25 mg/dl, respectively, during pregnancy, although the LDL receptor in this rabbit is genetically deficient. When Tyroxapol, which inhibits the degradation of very-low-density lipoprotein (VLDL), as well as Triton WR-1339, was injected into WHHL rabbits, the rate of the increase in serum cholesterol level in pregnant rabbits was not statistically different from that in non-pregnant rabbits. This result implied that the secretion rate of VLDL-cholesterol, the precursor of LDL-cholesterol, did not decrease during pregnancy. The amount of 125I-labeled LDL bound to LDL receptor was increased 1.8-fold in normal rabbits (from 29.3 +/- 4.3 to 52.3 +/- 4.6 ng/mg protein) and 12-fold in WHHL rabbits (from 0.5 +/- 0.2 to 6.0 +/- 0.7 ng/mg protein) during pregnancy. These results suggest that the decrease in serum cholesterol level in WHHL rabbits during pregnancy was associated with an increase in hepatic LDL receptor activity, which plays an important role in the regulation of serum cholesterol level.     

Paraoxonase activity is reduced by a pro-atherosclerotic diet in rabbits

Serum paraoxonase (PON1) is believed to protect against the development of atherosclerosis because of its ability to retard the oxidation of low-density lipoprotein (LDL) by hydrolysing LDL-associated phospholipid and cholesteryl-ester hydroperoxides. We have examined the relationship between PON1 and atherosclerosis development in transgenic rabbits overexpressing human apolipoprotein (apo) A-I and nontransgenic littermates fed a pro-atherogenic diet. PON1 activity was higher in transgenic (4006.1 +/- 716.7 nmol/min/ml) compared to control (3078.5 +/- 623.3 nmol/min/ml) rabbits (P < 0.01) while high-density lipoprotein (HDL) cholesterol was 1.84 +/- 0.54 mmol/L in transgenic rabbits and 0.57 +/- 0.21 mmol/L in control rabbits (P = 0.0001). After feeding rabbits a high-cholesterol diet for 14 weeks HDL-cholesterol fell by 70% in both transgenic and control rabbits (P < 0.001 compared to week 0) PON1 activity fell by 50% in both groups of rabbits (P < 0. 01 compared to week 0). The amount of thoracic aortic surface area covered by lesions was 29 +/- 16% in the control group and 26 +/- 15% in the transgenic group (P = NS). A pro-atherosclerotic diet reduces PON1 which may exaggerate the effects of the diet on the development of atherosclerosis.