scholarly journals Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
G. A. Bonaterra ◽  
K. Bender ◽  
B. Wilhelm ◽  
H. Schwarzbach ◽  
S. Metz ◽  
...  

Abstract Background Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date. Methods A group of rabbits received standard chow (SC) for 6 weeks (“negative control”; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified. Results After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells. Conclusions In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.

2013 ◽  
Vol 2 (1) ◽  
pp. 168 ◽  
Author(s):  
Brendon W. Smith ◽  
Jennifer L. King ◽  
Rita J. Miller ◽  
James P. Blue Jr. ◽  
Sandhya Sarwate ◽  
...  

<p>The cholesterol-fed rabbit is useful for atherosclerosis research. We describe development of a low-magnesium (Mg) cholesterol-containing diet to accelerate atherosclerosis in this model. Male New Zealand White rabbits were fed either chow or one of four atherogenic diets: 1% cholesterol 10% fat 0.11% Mg, 1% cholesterol 10% fat 0.40% Mg, 2% cholesterol 20% fat 0.11% Mg, or 2% cholesterol 20% fat 0.40% Mg. While feed intake decreased in cholesterol-fed rabbits, they were able to maintain their body weights. Rabbits consuming cholesterol experienced profound hypercholesterolemia and tissue lipid accumulation, with plasma cholesterol levels above 1500 mg/dl for all groups at the completion of the study. Liver and spleen lipid content and liver cholesterol content also increased. Aortic arch atheroma thickness was greatest in 1% cholesterol 10% fat 0.11% Mg animals. Tissue Mg levels decreased in cholesterol-fed animals compared to chow-fed controls, despite equal or greater serum Mg levels. Our results indicate that the 1% cholesterol 10% fat 0.11% Mg diet was optimal at promoting hypercholesterolemia and atherosclerosis while minimizing health complications for the animals. The low Mg cholesterol diet will be useful to other biomedical researchers interested in utilizing the rabbit for cardiovascular disease research.</p>


1959 ◽  
Vol 37 (1) ◽  
pp. 1069-1074 ◽  
Author(s):  
K. K. Carroll

Amphenone B was added in concentrations of 0.1 to 0.5% to a number of synthetic diets and to a fox chow diet. These were then fed to young male rats to determine the effects on adrenal weight and on the cholesterol content of the adrenals, liver, and plasma. The rats fed amphenone mixed with synthetic diets showed a greater increase in adrenal size and adrenal cholesterol than those fed amphenone mixed with the chow diet. The liver and plasma cholesterol values of rats fed amphenone on synthetic diets were also increased appreciably while those of rats fed amphenone in the chow diet were near normal. Synthetic diets containing erucic acid and amphenone appeared to have the greatest effect on adrenal size and cholesterol content but other synthetic diets in some cases caused a greater increase in liver and plasma cholesterol concentrations. An attempt to examine the effect of injected amphenone on cholesterol levels in rats fed different diets was limited by the fact that high doses of amphenone cause prolonged anesthesia.


1987 ◽  
Vol 58 (2) ◽  
pp. 257-263 ◽  
Author(s):  
K. Jaskiewicz ◽  
M. J. Weight ◽  
K. J. Christopher ◽  
A. J. S. Benadé ◽  
D. Kritchevsky

1. Two groups of vervet monkeys (Cercopithecus uethiops) were fed on high-cholesterol diets which differed only with respect to the protein source. In one group casein was the only protein source, while the other group received only soya-bean protein.2. Samples of blood, bile and liver biopsy material were collected at the commencement of the study and at 3-monthly intervals until termination 12 months later.3. At the end of the experimental period all the animals (n19) had high plasma cholesterol levels and had developed pigment gallstones, the compositions and weights of which were not related to the protein source or to plasma cholesterol levels. Gallstone weight was related to the presence of acidic and sulphated mucins in gallbladder mucosa. We were also unable to confirm the hypocholesterolaemic effect of soya-bean protein which has been demonstrated previously in rhesus monkeys and hamsters. Bile composition, and plasma lipids did not differ significantly between the casein-fed and soya-bean fed animals. Lithogenic index was below 1 for both groups and did not differ significantly between the two groups.4. No significant difference was found in the severity ofcholelithiasis between the casein-fed and the soya-bean-fed animals.


2012 ◽  
Vol 8 (3) ◽  
pp. 106
Author(s):  
Krisnansari Diah ◽  
Ariadne Tiara Hapsari ◽  
Evy Sulistyoningrum ◽  
Agus Prastowo

Background: Nowadays, cardiovascular disease caused by hypercholesterolemia has become the main cause of death. Propolis has been used widely to reduce plasma cholesterol levels.Objective: The aims of this research was to study the effect of propolis on lipid profile of hypercholesterolemic Sprague Dawley rats.Method: This was an experimental study with pre-post test. Twenty four (24) male Sprague Dawley rats aged 12-16 week old, weighing 125-200 g were allocated into 4 groups. Group I received standard meal + aquadest-gavage; group II received high cholesterol meal + PTU 0,01 + aquadest gavage; group III received high cholesterol meal + PTU 0,01 + 0,027 g propolis gavage; group IV received high cholesterol meal + PTU 0,01 + 0,054 g propolis gavage. Total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol levels before and after treatment were measured. The data were then analyzed with One Way Anova.Results: The study showed that there were no significant differences in changes of body weight. There were significant differences in total cholesterol levels between all groups of treatment. Triglyceride levels were significantly different among all groups, except between group I and IV. Furthermore, the HDL cholesterol levels of group I vs III and group I vs IV were significantly different. However, there were no differences found in LDL cholesterol levels among all groups of treatment.Conclusion: Provision of 0,027 g and 0,054 g propolis improve lipid profile (total cholesterol, triglyceride and HDL cholesterol levels) of hypercholesterolemic rats.


Author(s):  
Mei Hu ◽  
Sayantan Jana ◽  
Tolga Kilic ◽  
Faqi Wang ◽  
Mengcheng Shen ◽  
...  

Objective: Atherosclerosis is accumulation of lipids and extracellular matrix in the arterial wall. TIMPs (tissue inhibitor of metalloproteinases) can impact plaque deposition by regulating ECM (extracellular matrix) turnover. TIMP4 also influences lipid metabolism and smooth muscle cell (SMC) proliferation. We investigated the role of TIMP4 in atherosclerosis. Approach and Results: Mice lacking low-density lipoprotein receptor ( Ldlr −/− ) and Timp4 ( Timp4 −/− / Ldlr −/− ) were fed high-fat diet (HFD) or regular laboratory diet. After 3 or 6 months, HFD-fed male and female Timp4 −/− / Ldlr −/− mice exhibited higher plaque density in the abdominal aorta (but not in aortic valves, arch, thoracic aorta) compared with Ldlr −/− mice. Although plasma lipid and cholesterol levels were lower in Timp4 −/− / Ldlr −/− -HFD, cholesterol content in the abdominal aorta was higher along with elevated inflammatory cytokines, MMP (matrix metalloproteinase) activities, CD68 + /calponin + macrophage-like SMCs in Timp4 −/− / Ldlr −/− -HFD compared with Ldlr −/− -HFD mice. In vitro, oxidized LDL (low-density lipoprotein) markedly increased CD68 expression, reduced SMC markers, increased lipid uptake, and reduced cholesterol efflux protein ABCA1 (ATP-binding cassette transporter A1) in Timp4 −/− / Ldlr −/− compared with Ldlr −/− primary SMCs from abdominal, but not thoracic aorta. TIMP4 expression in the abdominal aorta (in vivo) and its corresponding SMCs (in vitro) was ≈2-fold higher than in the thoracic aorta and SMCs; TIMP4 levels decreased following HFD. Timp4 -deficiency in bone marrow–derived macrophages did not alter their foam cell formation capacity. Conclusions: TIMP4 protects against plaque deposition in the abdominal aorta independent of plasma cholesterol levels. TIMP4 prevents proteolytic degradation of ABCA1 in SMCs, hindering cholesterol accumulation and transdifferentiation to macrophage-like foam cells, representing a novel negative regulator of atherosclerosis.


1959 ◽  
Vol 37 (9) ◽  
pp. 1069-1074
Author(s):  
K. K. Carroll

Amphenone B was added in concentrations of 0.1 to 0.5% to a number of synthetic diets and to a fox chow diet. These were then fed to young male rats to determine the effects on adrenal weight and on the cholesterol content of the adrenals, liver, and plasma. The rats fed amphenone mixed with synthetic diets showed a greater increase in adrenal size and adrenal cholesterol than those fed amphenone mixed with the chow diet. The liver and plasma cholesterol values of rats fed amphenone on synthetic diets were also increased appreciably while those of rats fed amphenone in the chow diet were near normal. Synthetic diets containing erucic acid and amphenone appeared to have the greatest effect on adrenal size and cholesterol content but other synthetic diets in some cases caused a greater increase in liver and plasma cholesterol concentrations. An attempt to examine the effect of injected amphenone on cholesterol levels in rats fed different diets was limited by the fact that high doses of amphenone cause prolonged anesthesia.


2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Beiping Qiang ◽  
Jonathan Toma ◽  
Hiroko Fujii ◽  
Azriel Osherov ◽  
Nafiseh Nili ◽  
...  

Vein grafts (VG) account for more than 70% of conduits used in aortocoronary bypass surgery, but have high failure rates by 10 years. We have previously shown in an experimental model that VG undergo marked expansion by 4 weeks, which was followed by increased total LDL retention at 12 weeks. The objective of this study was to determine whether statin therapy would prevent these expansive remodelling changes. Methods and Results Reversed jugular vein-to-common carotid artery interposition graft were constructed in 24 cholesterol-fed (0.5%) rabbits. Rabbits were randomized to either control or atorvastatin (5 mg/kg/day) groups, starting two weeks prior to vein graft implantation and continuing until sacrifice at 1 or 12 weeks post-surgery. Ultrasound measurements of arterial luminal cross-sectional area (LCSA) were done at day 3 and at 4, 8 and 12 weeks post-surgery. Histomorphometric measurements were performed following sacrifice at 12 weeks. Atorvastatin treatment significantly decreased total plasma cholesterol levels at 12 weeks (6.70±4.19mmol/L vs placebo 38.65±10.55mmol/L, p<0.001). Atorvastatin significantly reduced expansive remodelling at all time points, including at 12 weeks (44.6±6.62mm 2 vs placebo 77.6±10.68mm 2 , p<0.001). Intimal CSA by histomorphometry was significantly reduced by atorvastatin at 12 weeks (5.59±2.19mm 2 vs placebo 9.57±2.43mm 2 , p<0.05). At 1 week, macrophage infiltration was significantly reduced (Ram11 positive intimal staining 0.018±0.019 vs 0.189±0.049, p<0.05). Atorvastatin treated samples at 1 week showed reduction in both MMP 2 activity (gelatin zymography) and metalloelastase activity (casein zymography). Conclusion: Atorvastatin prevents expansive remodelling in arterialized VG, likely through inhibition of macrophage infiltration and reduction of tissue proteolytic activity. This may be an important mechanism preventing VG atherosclerosis and late VG failure.


1973 ◽  
Vol 45 (5) ◽  
pp. 583-592 ◽  
Author(s):  
Gilbert R. Thompson ◽  
J. Paul Miller

1. Plasma lipids and lipoproteins have been studied in control subjects and patients with various types of steatorrhoea. 2. Low plasma cholesterol levels were found in malabsorbers and were associated with decreased amounts of low-density lipoprotein (LDL) in males and high-density lipoprotein (HDL) in females. 3. Serum triglyceride levels were normal in males, but exceeded control values in some of the females, due to an increase in very-low-density lipoprotein. 4. LDL composition was abnormal in both male and female malabsorbers, with a decreased proportion of cholesterol ester and an increased proportion of triglyceride. There was also an increased proportion of triglyceride in HDL. 5. These findings show that malabsorption markedly influences not only the concentration but also the composition of plasma lipoproteins.


2019 ◽  
Vol 20 (14) ◽  
pp. 3515 ◽  
Author(s):  
Jinjie Wang ◽  
Kunxiang He ◽  
Chun Yang ◽  
Xiao Lin ◽  
Xin Zhang ◽  
...  

Objective: Familial hypercholesterolemia (FH) is a dominant inherited disease caused mainly by low-density lipoprotein receptor (LDLR) gene mutations. To different extents, both heterozygous and homozygous FH patients develop premature coronary heart disease (CHD). However, most of the experimental animal models with LDLR deficiency could not fully recapitulate FH because they develop hyperlipidemia and atherosclerosis only in homozygous, but not in heterozygous, form. In the current study, we investigated the responsiveness of the LDLR+/− hamster to dietary cholesterol and whether plasma cholesterol levels were positively associated with the severity of atherosclerosis. Approach and Methods: wild type WT and LDLR+/− hamsters were fed a high fat diet with different cholesterol contents (HCHF) for 12 or 16 weeks. Plasma lipids, (apo)lipoproteins, and atherosclerosis in both the aorta and coronary arteries were analyzed. After a HCHF diet challenge, the levels of total cholesterol (TC) in WT and LDLR+/− hamsters were significantly elevated, but the latter showed a more pronounced lipoprotein profile, with higher cholesterol levels that were positively correlated with dietary cholesterol contents. The LDLR+/− hamsters also showed accelerated atherosclerotic lesions in the aorta and coronary arteries, whereas only mild aortic lesions were observed in WT hamsters. Conclusions: Our findings demonstrate that, unlike other rodent animals, the levels of plasma cholesterol in hamsters can be significantly modulated by the intervention of dietary cholesterol, which were closely associated with severity of atherosclerosis in LDLR+/− hamsters, suggesting that the LDLR+/− hamster is an ideal animal model for FH and has great potential in the study of FH and atherosclerosis-related CHD.


1981 ◽  
Vol 61 (4) ◽  
pp. 969-975 ◽  
Author(s):  
P. A. THACKER ◽  
M. O. SALOMONS ◽  
F. X. AHERNE ◽  
L. P. MILLIGAN ◽  
J. P. BOWLAND

Sixty-four crossbred pigs averaging 24 kg liveweight were used to study the effects of dietary propionic acid (PA) on plasma and tissue cholesterol concentrations of pigs fed hypercholesterolemic diets for 10 wk. Four diets, based on barley, wheat and soybean meal, consisting of a control diet and a diet containing 10% tallow, both fed with and without the addition of 5% PA were used in this study. Addition of PA to the control diet decreased feed intake (ADF) by 16%, decreased average daily gain (ADG) by 8% and improved feed conversion efficiency (FCE) by 8%. Addition of tallow to the control diet resulted in a 15% reduction in ADF, a 3% improvement in ADG and an 18% improvement in FCE. When both tallow and PA were present, ADF was depressed 26%, ADG decreased 5% and FCE improved 23%. The addition of tallow significantly increased the levels of total plasma cholesterol while the addition of PA significantly decreased the plasma cholesterol levels in comparison with the control diet and prevented the increase noted in the tallow group. Addition of PA to the control diet significantly increased the cholesterol content of backfat and significantly reduced the cholesterol content of the kidneys. Addition of PA to the tallow diet significantly reduced the cholesterol content of kidneys, but did not significantly affect the cholesterol content of backfat. It is suggested that the increased cholesterol content of backfat in pigs fed diets containing PA reflects a reduced transport of cholesterol from peripheral tissues to the liver for excretion in the bile.


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