Diet-induced Hypercholesterolemic Rabbits Research Articles

Synergistic effects of electronegative-LDL- and palmitic-acid-triggered IL-1β production in macrophages via LOX-1- and voltage-gated-potassium-channel-dependent pathways

Electronegative LDL (LDL(-)) and free fatty acids (FFAs) are circulating risk factors for cardiovascular diseases (CVDs) and have been associated with inflammation. Interleukin-1 beta (IL-1β) represents a key cytokine in the development of CVD; however, the initial trigger of IL-1β in CVD remains to be explored. In this study, we investigated the combined effects of LDL(-) from the plasma of ST-segment elevation myocardial infarction (STEMI) patients or diet-induced hypercholesterolemic rabbits and bovine serum albumin bound palmitic acid (PA-BSA) on IL-1β production in macrophages. Macrophages derived from THP-1 cells or human peripheral blood mononuclear cells were independently treated with LDL(-), PA-BSA or cotreated with LDL(-) and PA-BSA. The results showed that nLDL and/or PA-BSA had no effect on IL-1β, and LDL(-) slightly increased IL-1β; however, cotreatment with LDL(-) and PA-BSA resulted in abundant secretion of IL-1β in macrophages. Rabbit LDL(-) induced the elevation of cellular pro-IL-1β and p-Iκ-Bα, but PA-BSA had no effect on pro-IL-1β or p-Iκ-Bα. In potassium-free buffer, LDL(-)-induced IL-1β reached a level similar to that induced by cotreatment with LDL(-) and PA-BSA. Moreover, LDL(-) and PA-BSA-induced IL-1β was inhibited in lectin-type oxidized LDL receptor-1 (LOX-1) knockdown cells and by blockers of voltage-gated potassium (Kv) channels. LDL(-) from diet-induced hypercholesterolemic rabbit had a similar effect as STEMI LDL(-) on IL-1β in macrophages. These results show that PA-BSA cooperates with LDL(-) to trigger IL-1β production in macrophages via a mechanism involving the LOX-1 and Kv channel pathways, which may play crucial roles in the regulation of inflammation in CVD.

Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced Hypercholesterolemic rabbits

BackgroundAtherosclerosis is the most common disease of large and medium-sized arteries linked to oxidative stress, dyslipidemia as well as chronic inflammation. The aim of this study was to evaluate the potential health benefits of Baccaurea angulata (BA) fruit juice on the aorta of diet-induced hypercholesterolemic rabbits, to detect an accumulation of fatty streak and evaluate the percentage of atherosclerotic lesion accrued.MethodsThirty-five healthy male adults New Zealand White rabbits were assigned to seven different groups. Four groups were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL of BA fruit juice per kg of rabbit daily (atherogenic groups), while the other three groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg of rabbit daily (normocholesterolemic groups) for 90 days. The thoracic and abdominal aorta between the heart origin and bifurcation into iliac arteries of all the rabbits were carefully removed and analyzed accordingly.ResultsThe supplementation of the high-cholesterol diet of hypercholesterolemic rabbits with only 0.5 mL BA/kg rabbit per day significantly (p < 0.001) improved aortic lipid profile, attenuated aortic fatty streak development and reduced intima thickening. Higher BA doses used (1.0 and 1.5 mL/kg rabbit per day) also significantly (p < 0.001) decreased further the development of aortic fatty streaks, reduced the thickening of the tunica intima layer and preserved endothelial healing following arterial injury.ConclusionTherefore, BA fruit is a potential novel functional food with effective anti-inflammatory, anti-atherogenic and hypocholesterolemic activities.

Baccaurea angulata fruit juice ameliorates altered hematological and biochemical biomarkers in diet-induced hypercholesterolemic rabbits

Hypercholesterolemia is an important risk factor linked to the alteration of blood hematology and clinical chemistry associated with the development and progression of atherosclerosis. Previous studies have demonstrated the safety and potential health benefits of Baccaurea angulata (BA) fruit. We hypothesized that the oral administration of BA fruit juice could ameliorate the alteration in the hematological and biochemical biomarkers of diet-induced hypercholesterolemic rabbits. The aim of this study was to investigate the effects of different doses of BA juice on the hematological and biochemical biomarkers in normo- and hypercholesterolemic rabbits. Thirty-five healthy adult New Zealand White rabbits were assigned to seven different groups for 90days of diet intervention. Four atherogenic groups were fed a 1% cholesterol diet and 0, 0.5, 1.0, and 1.5mL of BA juice per kg of rabbit daily. The other three normal groups were fed a commercial rabbit pellet diet and 0, 0.5, and 1.0mL of BA juice per kg of rabbit daily. Baseline and final blood samples after 90days of repeated administration BA juice were analyzed for hematological parameters while serum, aortic and hepatic lysates were analyzed for lipid profiles and other biochemical biomarkers. The alteration of the hemopoietic system, physiological changes in serum and tissues lipid profiles and other biochemicals resulting from the consumption of a high-cholesterol diet were significantly (P<.05) ameliorated by the administration of BA juice. Improvements of the biomarkers in rabbits were dose-dependent, markedly enhanced at the highest dose of juice (1.5mL/kg/day). The results suggest potential health benefits of the antioxidant-rich BA fruit juice against hypercholesterolemia-associated hematological and biochemical alterations in the rabbit.

Proteomic analysis of differential protein expression in high fat diet-induced hypercholesterolemic rabbits

Aim: Atherosclerosis is the major cause of mortality worldwide. Much attention has been focused on the use of herbal natural products to cure this disease. Using a proteomic approach the present study evaluated cardio-protective effects of Terminalia arjuna extract (TAE) on differential protein expression in hypercholesterolemic rabbits.

Temporal and Quantitative Analysis of Atherosclerotic Lesions in Diet-Induced Hypercholesterolemic Rabbits

The diet-induced atherosclerotic rabbit is an ideal model for atherosclerosis study, but temporal changes in atherosclerotic development in hypercholesterolemic rabbits are poorly understood. Japanese white rabbits were fed a high-cholesterol diet to induce sustained hypercholesterolemia, and each group of 10–12 animals was then sacrificed at 6, 12, 16, or 28 weeks. The rabbit aortas were harvested, and the sizes of the gross and intima atherosclerotic lesions were quantified. The cellular component of macrophages (Mφs) and smooth muscle cells (SMCs) in aortic intimal lesions was also quantified by immunohistochemical staining, and the correlation between plasma cholesterol levels and the progress of atherosclerotic lesions was studied. The ultrastructure of the atherosclerotic lesions was observed by transmission electron microscopy (TEM). Widely variable atherosclerotic plaques were found from 6 weeks to 28 weeks, and the lesional progress was closely correlated with cholesterol exposure. Interestingly, a relatively reduced accumulation of Mφ, an increased numbers of SMCs, and a damaged endothelial layer were presented in advanced lesions. Moreover, SMCs were closely correlated with cholesterol exposure and lesional progress for the whole period. Cholesterol exposure directly determines atherosclerotic progress in a rabbit model, and the changes in the cellular component of advanced lesions may affect plaque stability in an atherosclerotic rabbit model.

Hypercholesterolemia impaired sperm functionality in rabbits.

Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events.

The Role of Dates (Phoenix dactylifera) Aqueous Extract in Improving the Plasma Lipid Profiles of Diet-Induced Hypercholesterolemic Rabbits

The Role of Dates (Phoenix dactylifera) Aqueous Extract in Improving the Plasma Lipid Profiles of Diet-Induced Hypercholesterolemic Rabbits

Effects of grape pomace on the antioxidant defense system in diet-induced hypercholesterolemic rabbits.

The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing H2O2 that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia.

Hyaluronan forms complexes with low density lipoprotein while also inducing foam cell infiltration in the dermis

Xanthoma is a foam cell infiltrating lesion similar to atherosclerosis. Glycosaminoglycans and proteoglycans have long been considered to play a role in atherogenesis. The purpose of this study is to investigate the role of hyaluronan, the main dermal glycosaminoglycan, in xanthoma formation. The complex formation of low density lipoprotein (LDL) with hyaluronan was investigated by assaying the cholesterol level of precipitates that were formed by incubating LDL, hyaluronan and cetylpyridinium chloride in the presence of Ca2+. The uptake of LDL by mouse peritoneal macrophages was studied by assaying the cellular cholesterol esterification activity. The responsible receptor for the LDL internalization was examined by saturating hyaluronan receptor and blocking class A macrophage scavenger receptor (CD204). Hyaluronan was injected into the dorsal skin of diet-induced hypercholesterolemic rabbits to reveal the xanthoma inducing activity of hyaluronan. Cetylpyridinium chloride precipitated hyaluronan, which had formed complexes with LDL. The macrophages incorporated hyaluronan-LDL complexes and oxidized LDL via CD204. Foam cell infiltration and cholesterol accumulation were induced by intradermal injections of hyaluronan in diet-induced hypercholesterolemic rabbits. Hyaluronan, like other sulfated glycosaminoglycans, retains LDL by forming a complex. Via macrophage scavenger receptors, macrophages incorporate not only LDL-hyaluronan complexes, but also oxidized LDL, which has been oxidized during the retention time.

Oren-gedoku-to and Keishi-bukuryo-gan-ryo Inhibit the Progression of Atherosclerosis in Diet-Induced Hypercholesterolemic Rabbits

In this study, we examined whether the Kampo formulas Oren-gedoku-to (OGT, Huanglian-jie-du-tang in Chinese) and Keishi-bukuryo-gan-ryo (KBG, Gui-zhi-fu-ling-wan in Chinese) could prevent the progression of atherosclerosis in cholesterol-fed rabbit, an animal model for hypercholesterolemia in vivo. Twenty-four male Japanese white rabbits (2 kg body weight) were divided into four groups. The control group was fed standard rabbit chow containing 1% cholesterol, the OGT group was fed standard rabbit chow containing 1% cholesterol and 1% OGT, the KBG group was fed standard rabbit chow containing 1% cholesterol and 1% KBG, and the vitamin E group was fed standard rabbit chow containing 1% cholesterol and vitamin E (450 mg/1000 g). All four groups were kept on these diets for 8 weeks. At the end of the experiments, the percentage of surface area of the total thoracic aorta with visible plaque was significantly reduced in the OGT and KBG groups. The serum thiobarbituric acid reactive substances of the vitamin E group showed a significantly low value compared with the control group, whereas the serum lipid peroxide levels of the OGT and KBG groups were considerably lower than that of the control groups as well as that of the vitamin E group. Furthermore, the urinary 8-hydroxydeoxyguanosine levels of the OGT and KBG groups were considerably lower than that of the vitamin E group. These results suggest that OGT and KBG prevent the progression of atheromatous plaque by creating a sounder antioxidant defense system than vitamin E.

Polygonatum rhizoma affects antioxidant defense systems without changing mRNA expression in diet-induced hypercholesterolemic rabbits.

This study was conducted to determine the antioxidant effects of a Polygonatum extract compared with the major antioxidant, vitamin E, in rabbits fed a high-cholesterol diet. Rabbits were given a high-cholesterol (0.5%, wt/wt) diet with vitamin E (0.03%, wt/wt) or a Polygonatum extract (0.05%, wt/wt) for 8 weeks. The body weight gain (g/week) was only significantly increased only in the high-cholesterol-fed control group, yet the relative liver weight was significantly lower in the Polygonatum group compared with the other groups. The supplementation of vitamin E and Polygonatum extract led to an increase in the hepatic catalase (CAT) activity without any change in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Hepatic total glutathione content was significantly higher in the Polygonatum group than in the other groups. The level of hepatic mitochondrial H(2)O(2) was significantly lower in the two supplemented groups compared with the control group, whereas the level of cytosolic H(2)O(2) was only significantly lower in the Polygonatum group than in the control group. The level of plasma thiobarbituric acid-reactive substances (TBARS) was only significantly lower in the vitamin E group, whereas the level of hepatic TBARS was slightly lower in the Polygonatum group than in the other groups. In the case of the high-density lipoprotein-related antioxidant enzyme, vitamin E supplementation produced the highest plasma paraoxonase (PON) activity compared with the other groups, although there was no difference in the hepatic PON activity among the groups. Meanwhile, the plasma vitamin E concentration was significantly higher in the vitamin E and Polygonatum groups than in the control group; however, plasma vitamin A concentration did not differ significantly between the groups. As regards the mRNA expressions of hepatic antioxidant enzymes, the vitamin E and Polygonatum extract supplementation had no effect on the SOD, CAT, GSH-Px, and PON mRNA expression. Accordingly, these results indicate that the Polygonatum extract had a positive effect on the antioxidant defense system based on decreasing the content of hepatic TBARS and hydrogen peroxide, increasing the CAT activity and total glutathione level in the liver, and sparing the plasma vitamin E. Thus, further studies on the functional components in Polygonatum extract and their biological efficacies are needed.

&lt;I&gt;Polygonatum&lt;/I&gt; Rhizoma Affects Antioxidant Defense Systems Without Changing mRNA Expression in Diet-Induced Hypercholesterolemic Rabbits

&lt;I&gt;Polygonatum&lt;/I&gt; Rhizoma Affects Antioxidant Defense Systems Without Changing mRNA Expression in Diet-Induced Hypercholesterolemic Rabbits

Brain region-dependent increases in beta-amyloid and apolipoprotein E levels in hypercholesterolemic rabbits.

Recent studies indicate a possible link between serum cholesterol level, beta-amyloid (Abeta) peptide concentrations, and the incidence of Alzheimer's disease (AD). In the present report, the effects of dietary cholesterol on Abeta and apolipoprotein E (APOE) levels in several brain regions were examined using diet-induced hypercholesterolemic rabbits as the animal model. Increased dietary cholesterol levels increased Abeta concentrations in temporal cortex (p = 0.02). A similar trend was observed in the frontal cortex (p = 0.06), yet not in the cerebellum. Interestingly, the regional levels of Abeta in the hypercholesterolemic rabbit paralleled the amyloid pathology observed in AD brain. Elevated APOE levels were also noticed in temporal (p < 0.01) and frontal (p < 0.01) cortices, but not in cerebellum, in the rabbit fed with cholesterol-abundant diet. These results suggest that high serum cholesterol levels could induce the elevation of brain APOE, which may play a role in aggravating the Abeta accumulation.

P1644 Increased microvascular permeability in diet-induced hypercholesterolemic rabbits: a magnetic resonance imaging-based longitudinal study

P1644 Increased microvascular permeability in diet-induced hypercholesterolemic rabbits: a magnetic resonance imaging-based longitudinal study

Effects of fish oil and vitamin E on the antioxidant defense system in diet-induced hypercholesterolemic rabbits

This study was designed to investigate the effects of fish oil and vitamin E on the antioxidant defense system in hypercholesterolemic rabbits. A high fat and cholesterol diet, with or without supplement by fish oil and/or a vitamin E supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of regular laboratory rabbit chow, a high fat and cholesterol-enriched diet increased atheroma formation, plasma lipid and peroxide levels, decreased blood glutathione levels, and reduced plasma glutathione reductase, glutathione peroxidase, and catalase activities. Fish oil supplementation significantly reduced atheroma and increased glutathione reductase and glutathione peroxidase activities and blood glutathione levels, but increased plasma lipid peroxide levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels. These results indicate that a high fat and cholesterol diet attenuates blood glutathione levels and plasma antioxidant enzyme activities, which may account for some of its atherogenic properties. Consumption of fish oil enhances antioxidative defenses against the oxidative stress imposed by hypercholesterolemia, and vitamin E further enhances these beneficial effects.

The role of vitamin E on the anti-atherosclerotic effect of fish oil in diet-induced hypercholesterolemic rabbits

The role of vitamin E on the anti-atherosclerotic effect of fish oil in diet-induced hypercholesterolemic rabbits was studied in male New Zealand white rabbits. The animals were randomly divided into six groups of 14 each according to the chow given them. Group I, control, rabbits were fed regular laboratory rabbit chow. In addition to the regular chow, Group II rabbits were fed a high (1%) cholesterol-enriched diet. Group III had the same diet as Group II plus 450 mg vitamin E/1000 g chow. Group IV also had the same diet as Group II plus 10% fish oil, but without vitamin E. Group V’s diet contained 1% cholesterol, 10% fish oil, and 450 mg vitamin E/1000 g chow. Group VI had the same diet as Group V, but with 150 mg vitamin E/1000 g chow. At the end of a 6-week feeding, the ascending aorta from seven rabbits from each group was harvested for the analysis of prostanoid production, thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity, and cholesterol and vitamin E levels; the same tissue from the other seven rabbits from each group was obtained for the delineation of atherosclerotic lesions by planimetry after the Sudan IV stain. The high cholesterol diet-treated rabbits had worse prostanoid synthesis and higher TBARS levels, which paralleled the severity of the atherosclerosis. Vitamin E or fish oil supplementation in a high cholesterol diet had beneficial prostanoid production, reduced aortic TBARS levels, and attenuated atherosclerotic lesions; these effects were potentiated when vitamin E and fish oil were combined together. The atherosclerotic lesion reduction in rabbits treated with high cholesterol plus fish oil and 450 mg vitamin E/1000 g chow reached statistical significance ( P < 0.05) compared to high cholesterol and the same dose of vitamin E-treated rabbits. The rabbits treated with high cholesterol plus fish oil, but without vitamin E or with 150 mg vitamin E/1000 g chow showed an increased plasma creatine kinase activity at 4 ( P < 0.01 and 0.05, respectively) and 6 ( P < 0.001 and 0.01, respectively) week of feeding. These results suggest that vitamin E and/or fish oil attenuate atherosclerosis in high cholesterol-fed rabbits; vitamin E and fish oil potentiated the effect of each other. Furthermore, without sufficient vitamin E supplementation, rabbits treated with high cholesterol plus fish oil will show an elevation of plasma creatine kinase activity.

Vitamin E supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits

The effects of vitamin E supplementation in a dose of 450 mg/1000 g chow on the myointimal proliferation of the abdominal aorta after balloon injury were studied in 4 groups of rabbits (24 each). The animals were fed regular diet, regular diet plus vitamin E, 1% cholesterol-enriched diet, and 1% cholesterol-enriched diet plus vitamin E. Each animal underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 8 balloon-injured and 8 sham-operated animals of each group, the abdominal aortas were harvested 3 days after the procedure for the analysis of prostacyclin and thromboxane A 2 synthesis, thiobarbituric acid reactive substances (TBARS) levels, enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GP) as well as reduced (GSH) and oxidized (GSSG) glutathione levels, 3H-thymidine uptake, cholesterol as well as vitamin E contents. In the other 8 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for the morphometric study. In dependent of high cholesterol feeding, the vitamin E-treated rabbits had lower aortic production of thromboxane B 2, higher 6-keto-PGF 1α and higher 6-keto-PGF 1α/thromboxane B 2 ratios in both procedures. The aortic TBARS levels of the rabbits treated high cholesterol alone were significantly higher than the other three groups in both procedures. Balloon injury had a trend to increase TBARS levels and had significantly higher 3H-thymidine uptake (each p < 0.001) than sham operation in each group. Vitamin E supplement to high cholesterol diet or regular chow reduced aortic TBARS levels ( p < 0.005 and 0.01, respectively) and 3H-thymidine uptake ( p < 0.05 and 0.01, respectively), as well as attenuated myointimal proliferation of the abdominal aorta and left common iliac artery after balloon injury; but only supplement to high cholesterol diet reached statistical significances (both p < 0.05 compared to rabbits fed high cholesterol alone). These results suggest that vitamin E supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation of the abdominal aortic wall, thus attenuates myointimal proliferation after balloon injury; these presentations are particularly obvious in diet-induced hypercholesterolemic rabbits.

A peptide from hog plasma that inhibits human cholesteryl ester transfer protein

A peptide that inhibits the human cholesteryl ester transfer protein (CETP) was isolated from hog plasma by ultracentrifugation, two sequential column chromatographies and electroelution from gels. Molecular weight of the peptide was determined to be approximately 3 kDa on the SDS–PAGE. The peptide contained 28 amino acids with an identical sequence to the amino terminus of hog apolipoprotein-CIII except two amino acid residues: –Pro–Glu– at the fifth and sixth amino acids from the amino terminus in the isolated peptide, in contrast to –Leu–Leu– in hog apo-CIII. A peptide synthesized chemically according to the amino acid sequence of the peptide (designated P 28) showed approximately the same degree of CETP inhibitory activity as the isolated peptide. Synthetic peptides with different number of amino acids were also tested for CETP inhibition. Among the peptides, the one with 20 amino acid residues (P 20) from the amino terminus showed the highest inhibitory activity against the CETP. The peptide appeared to be associated with the hog high-density lipoproteins (HDL), as determined by immunoblot analysis using antibody against P 28. The CETP-inhibitory activity of the peptide was examined in vivo using diet-induced hypercholesterolemic rabbits. When the peptide was injected into the rabbits (7–9 mg/kg body weight), approximately 75% CETP activity disappeared from the plasma in 1 h after the injection and the effect lasted up to 30 h. The inhibition of CETP in vivo led to a concomitant decrease in total plasma cholesterol level up to 30% and an increase in the level of HDL-cholesterol up to 32%. The cholesterol concentrations in the rabbit plasma gradually recovered to the initial level after 48 h.

Comparison of aging and hypercholesterolemic effects on the sodium inward currents in cardiac myocytes

To study and to compare the hypercholesterolemic and aging effect on the sodium inward currents (I Na) in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocyte isolated from normo- and dietinduced hypercholesterolemic rabbits of different age groups. The cell capacitance of adult and hyperlipidemic myocytes seemed larger than that of young and normolipidemic ones. However, the sodium current density at a holding potential of -80 mV on adult and hypercholesterolemic ventricular sarcolemma was significantly lower than that on young and normolipidemic one (adult hyperlipidemic: −15.3 ± 2.4 pA pF (n = 16), adult control: −28.1 ± 3.4 pA pF (n = 13), young hyperlipidemic: − 39.5 ± 5.4 pA pF (n = 19), young control: −67.3 ± 7.8 pA pF (n = 12)). In aging process, this effect was due to a decrease in channel number, a leftward shift in the inactivation potential and a slowing of the time course of recovery. In hypercholesterolemia, however, the major cause was due to the functional change of sodium currents. In addition to decreasing the sodium current magnitude, hypercholesterolemia lowered the threshold for excitation of cardiac myocytes (−50 mV vs −40 mV). In conclusion, aging process depressed the sodium channel activity in ventricular myocytes. In addition to inducing some similar functional alterations of I Na as aging process, long-term hypercholesterolemia could also increase the excitability in cardiac myocytes, which was different from aging process.

Fish oil supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits

The effects of supplementing with fish oil on the myointimal proliferation of the abdominal aorta after balloon injury were studied in control and in rabbits fed a 1% cholesterol-enriched diet, with and without 10% fish oil supplementation. Twenty-one animals in each group underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 7 balloon-injured and 7 sham-operated animals of each group, the abdominal aorta was harvested 3 days later for the analysis of prostanoids, malondialdehyde, superoxide dismutase activity, [ 3H]thymidine uptake, and cholesterol levels. In the other 7 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for morphometric study. The fish oil-treated rabbits had the lowest aortic production of thromboxane B 2 levels and the highest 6-keto-PGF 1α/thromboxane B 2 ratios among the three groups after balloon injury. The aortic malondialdehyde levels of the cholesterol-fed rabbits were significantly higher than the other two groups (each P < 0.001) independent of balloon injury. The myointimal proliferation of the abdominal aorta and left common iliac artery in the fish oil-treated rabbits was less severe than in the cholesterol-fed animals (both P < 0.001) and was comparable with the controls. These results suggest that a fish oil supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation on the abdominal aortic wall, thus attenuating myointimal proliferation after balloon injury in diet-induced hypercholesterolemic rabbits.