Comparison of the effects of fish oil and olive oil on blood lipids and aortic atherosclerosis in Watanabe heritable hyperlipidaemic rabbits

To compare the effects of fish oil and olive oil on the development of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits, 6-week-old animals were given a daily dose (1·5 ml/kg body weight) of fish oil (n 10) or olive oil (n 10) by oral administration for 16 weeks. Plasma cholesterol and triacylglycerols were measured once monthly, and their concentrations in lipoproteins, together with susceptibility of LDL to oxidation were measured in vitro at the termination of the experiment. Aortic atherosclerosis was quantified biochemically and microscopically. After 4 weeks of treatment, and throughout the study thereafter, blood lipids were significantly (P < 0·05) lower in the fish-oil group than in the olive-oil group (cholesterol: 17·0 v. 30·3 mmol/l, triacylglycerols 2·97 v. 6·25 mmol/l, at termination). In the fish-oil group cholesterol was significantly lower in intermediate-density lipoproteins (2·69 v. 6·76 mmol/l) and VLDL (3·36 v. 11·51 mmol/l). Triacylglycerol levels of intermediate-density lipoproteins and VLDL in the fish-oil group were also significantly lower when compared with the olive-oil group (0·54 v 1·36 mmol/l and 0·92 v. 2·87 mmol/l respectively). No group differences were recorded for LDL- and HDL-cholesterol or triacylglycerol levels. A significantly higher oxidation of LDL was recorded 1 h after exposure to CuSO4 in the fish-oil group when compared with the olive-oil group (0·465 v. 0·202, arbitrary units). The following indicators of atherosclerosis development were significantly lower in the fish-oil group than in the olive-oil group: the cholesterol content (mg/g tissue) in the ascending aorta (29·8 v.48·9), the intima:media value (4·81 v. 18·24) and the area of intima (0·10 v. 0·57 mm2) in the thoracic aorta. It was concluded that fish-oil treatment decreased blood lipids and the development of aortic atherosclerosis in WHHL rabbits when compared with olive-oil treatment.

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Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽

10.1024/0301-1526.34.1.11 ◽

2005 ◽

Vol 34 (1) ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

Brunner-La Rocca ◽

Schindler ◽

Schlumpf ◽

Saller ◽

Suter

Keyword(s):

Endothelial Dysfunction ◽

Blood Lipids ◽

Ex Vivo ◽

Hdl Cholesterol ◽

Blood Lipid ◽

Tibetan Medicine ◽

Double Blind ◽

Intraarterial Infusion ◽

Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

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Antithrombotic and Antiatherosclerotic Properties of Olive Oil and Olive Pomace Polar Extracts in Rabbits

Mediators of Inflammation ◽

10.1155/2007/36204 ◽

2007 ◽

Vol 2007 ◽

pp. 1-11 ◽

Cited By ~ 43

Author(s):

Nektaria Tsantila ◽

Haralabos C. Karantonis ◽

Despina N. Perrea ◽

Stamatios E. Theocharis ◽

Dimitrios G. Iliopoulos ◽

...

Keyword(s):

Olive Oil ◽

Polar Lipid ◽

Olive Pomace ◽

Experimental Time ◽

Group A ◽

Atherosclerosis Development ◽

Potent Antagonist ◽

Induced Aggregation ◽

Early Atherosclerosis

Olive oil polar lipid (OOPL) extract has been reported to inhibit atherosclerosis development on rabbits. Olive pomace polar lipid (PPL) extract inhibits PAF activity in vitro and the most potent antagonist has been identified as a glycerylether-sn-2-acetyl glycolipid with common structural characteristics with the respective potent antagonist of OOPL. The aim of this study was to investigate the effect of PPL on early atherosclerosis development on rabbits and to compare it with the antiatherosclerotic effect of OOPL. OOPL and PPL inhibition potency, towards both PAF action and PAF binding, was tested in vitro on washed rabbit platelets. Consequently, rabbits were divided into three groups (A, B, and C). All groups were fed atherogenic diet for 22 days. Atherogenic diets in groups B and C were enriched with OOPL and PPL, respectively. At the end of the experimental time, rabbits were euthanized and aortic samples were examined histopathologically. OOPL and PPL inhibited PAF-induced aggregation, as well as specific PAF binding, with PPL being more potent. Free and bound PAF levels and PAF-AH activity were significantly elevated at the end of the experimental time. Plasma total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides levels were also found increased. Groups B and C exhibited significantly increased values of EC50compared to group A. Histopathological examination revealed that the development of early atherosclerosis lesions in groups B and C were significantly inhibited compared to group A. Significant differences were noted in the early atherosclerosis lesions between groups B and C, thus indicating that PPL exhibit its anti-atherosclerotic activity by blocking PAF receptor. Specific PAF antagonists with similar in vitro and in vivo bioactivity to those that have been previously reported in OOPL exist in PPL.

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Platelet ABCA1 Expression Is Normal in Scott Syndrome Dogs.

Blood ◽

10.1182/blood.v108.11.3918.3918 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3918-3918 ◽

Cited By ~ 2

Author(s):

James L. Catalfamo ◽

Marjory B. Brooks ◽

Melanie Ammersbach ◽

Amanda K. DeMaster

Keyword(s):

Plasma Cholesterol ◽

Hdl Cholesterol ◽

Cholesterol Content ◽

Tangier Disease ◽

German Shepherd ◽

Virtual Absence ◽

Significant Difference ◽

Abca1 Expression ◽

Induced Aggregation ◽

Stimulation Control

Abstract Scott syndrome is a rare platelet function defect characterized by a failure of Ca2+-stimulated phosphatidylserine (PS) externalization and lack of platelet prothrombinase activity. In 2005 Albrecht et al. (Blood 106:542) described low levels of ATP-binding transporter A1 (ABCA1) mRNA in lymphocytes and heterozygosity for a novel ABCA1 missense mutation in a patient with Scott Syndrome. The proband’s expression of platelet ABCA1, however, was not measured. Platelet dysfunction has been described as a feature of Tangier disease, a monogenic disorder caused by ABCA1 mutations (Nofer et al, JBC279:34032, 2004). The disease phenotype results from altered lipid trafficking, with a virtual absence of plasma HDL cholesterol and accumulation of lipid in cells of the RE system. In the current study, we systematically evaluated platelets from Scott syndrome dogs to find evidence of ABCA1 deficiency. Platelets from control dogs and affected German shepherd dogs (GSD) were compared with regard to cholesterol content, ABCA1 protein expression, and reactivity to collagen, convulxin (CVX), and thrombin. All GSD had normal plasma cholesterol and triglyceride levels, with no significant difference in mean platelet cholesterol content from that of control dogs (control cholesterol = 13.4 ug/108 platelets, GSD cholesterol = 12.6 ug/108 platelets; n= 6; p = 0.726). Western blot analysis of platelet extracts from control dogs and GSD using a polyclonal antibody to human ABCA1 revealed comparable levels of a 220 kD protein band, the expected size for human ABCA1. We found no significant differences in maximal platelet aggregation in response to 12 ug/mL collagen stimulation [control dog mean response = 82.9% (n=10), GSD = 75.0 % (n= 7); p = 0.133)]. CVX concentration-response aggregation curves obtained for washed platelets were similar for control dogs (n=4) and GSD (n=3) in the range of 1 to 100 nM CVX, with a plateau of maximal aggregation at 10 nM CVX. In flow cytometry analyses, we found no difference in mean platelet mepacrine uptake between control dogs and GSD (mean positive platelets = 64%, n= 3 control, n=5 GSD). There were no significant differences in mean CD62P expression post-thrombin (0.5 U/mL) or CVX (2 nM) stimulation [control CD62P positive platelets post-thrombin = 57%, post-CVX = 47.5% (n=7); GSD CD62P positive platelets post-thrombin = 49%, post-CVX = 56% (n=4)]. Although ABCA1 has been proposed to play a role in PS transport, we found no evidence of ABCA1 deficiency and none of the characteristic platelet abnormalities associated with Tangier disease in canine Scott syndrome, a model of impaired transmembrane PS movement. Comparison of Platelet Phenotypes ANALYSIS TANGIER DISEASE SCOTT SYNDROME GSD Ionophore induced PS expression Present Absent Collagen or CVX induced aggregation Decreased Normal CVX or thrombin induced alpha granule release Decreased Normal Platelet ABCA1 expression Absent Present

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Relationship between HDL Cholesterol Efflux Capacity, Calcium Coronary Artery Content, and Antibodies against ApolipoproteinA-1 in Obese and Healthy Subjects

Journal of Clinical Medicine ◽

10.3390/jcm8081225 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1225 ◽

Cited By ~ 6

Author(s):

Nicolas Vuilleumier ◽

Sabrina Pagano ◽

Fabrizio Montecucco ◽

Alessandra Quercioli ◽

Thomas H. Schindler ◽

...

Keyword(s):

Coronary Artery ◽

Cholesterol Efflux ◽

Positive Association ◽

Hdl Cholesterol ◽

Cholesterol Content ◽

Cholesterol Efflux Capacity ◽

Clinical Observations ◽

Framingham Risk ◽

Obese Subjects

Aims: To explore the associations between cholesterol efflux capacity (CEC), coronary artery calcium (CAC) score, Framingham risk score (FRS), and antibodies against apolipoproteinA-1 (anti-apoA-1 IgG) in healthy and obese subjects (OS). Methods and Results: ABCA1-, ABCG1-, passive diffusion (PD)-CEC and anti-apoA-1 IgG were measured in sera from 34 controls and 35 OS who underwent CAC score determination by chest computed tomography. Anti-apoA-1 IgG ability to modulate CEC and macrophage cholesterol content (MCC) was tested in vitro. Controls and OS displayed similar ABCG1-, ABCA1-, PD-CEC, CAC and FRS scores. Logistic regression analyses indicated that FRS was the only significant predictor of CAC lesion. Overall, anti-apoA-1 IgG were significantly correlated with ABCA1-CEC (r = 0.48, p < 0.0001), PD-CEC (r = −0.33, p = 0.004), and the CAC score (r = 0.37, p = 0.03). ABCA1-CEC was correlated with CAC score (r = 0.47, p = 0.004) and FRS (r = 0.18, p = 0.29), while PD-CEC was inversely associated with the same parameters (CAC: r = −0.46, p = 0.006; FRS: score r = −0.40, p = 0.01). None of these associations was replicated in healthy controls or after excluding anti-apoA-1 IgG seropositive subjects. In vitro, anti-apoA-1 IgG inhibited PD-CEC (p < 0.0001), increased ABCA1-CEC (p < 0.0001), and increased MCC (p < 0.0001). Conclusions: We report a paradoxical positive association between ABCA1-CEC and the CAC score, with the latter being inversely associated with PD in OS. Corroborating our clinical observations, anti-apoA-1 IgG enhanced ABCA1 while repressing PD-CEC, leading to MCC increase in vitro. These results indicate that anti-apoA-1 IgG have the potential to interfere with CEC and macrophage lipid metabolism, and may underpin paradoxical associations between ABCA1-CEC and cardiovascular risk.

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In vitro characterization of two types of ldl apheresis module and effect of repetitive LDL apheresis on plasma cholesterol levels and aortic atherosclerosis in heterozygous whhl rabbits.

Japanese Circulation Journal ◽

10.1253/jcj.55.68 ◽

1991 ◽

Vol 55 (1) ◽

pp. 68-80

Author(s):

Soo-Soo Kim ◽

Yasunori Kutsumi ◽

Tsuguhiko Nakai ◽

Susumu Miyabo

Keyword(s):

Plasma Cholesterol ◽

Aortic Atherosclerosis ◽

Ldl Apheresis ◽

Cholesterol Levels ◽

In Vitro Characterization

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Effect of oat saponins on plasma and liver lipids in gerbils (Meriones unguiculatus) and rats

British Journal Of Nutrition ◽

10.1079/bjn19950029 ◽

1995 ◽

Vol 73 (2) ◽

pp. 275-286 ◽

Cited By ~ 14

Author(s):

G. Önning ◽

N.-G. Asp

Keyword(s):

Plasma Cholesterol ◽

Liver Lipid ◽

Hdl Cholesterol ◽

Liver Weight ◽

Cholesterol Content ◽

Meriones Unguiculatus ◽

Liver Cholesterol ◽

Control Group ◽

Liver Lipids ◽

Plasma And Liver Lipids

The effects of oat saponins (a mixture of avenacosides A and B) on plasma and liver lipids in gerbils (Meriones unguiculatus) and rats were investigated. Cholesterol-containing diets high in total and saturated fat and with different avenacoside contents (zero (ethanol-extracted oats), normal (oats) and twice normal (ethanol-extracted oats plus added avenacosides)) were used. Compared with a cellulose control group the oat diets in both species gave a significantly higher cholesterol content in the HDL fraction and a significantly lower liver cholesterol content. No significant differences in total plasma cholesterol, HDL-cholesterol and plasma triacylglycerols were found, however, between the groups fed on oats with different avenacoside content. The liver weight, total liver cholesterol and free liver cholesterol were also similar, whereas the liver lipid content was significantly lower in rats given the highest amount of avenacosides compared with zero or normal amounts. The tendency was the same in gerbils. Thus, the oat saponins had only minor effects on lipid metabolism in gerbils and rats.

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Phenol-Enriched Virgin Olive Oil Promotes Macrophage-Specific Reverse Cholesterol Transport In Vivo

Biomedicines ◽

10.3390/biomedicines8080266 ◽

2020 ◽

Vol 8 (8) ◽

pp. 266

Author(s):

Lídia Cedó ◽

Sara Fernández-Castillejo ◽

Laura Rubió ◽

Jari Metso ◽

David Santos ◽

...

Keyword(s):

Olive Oil ◽

Reverse Cholesterol Transport ◽

Cholesterol Efflux ◽

Ex Vivo ◽

Virgin Olive Oil ◽

Hdl Cholesterol ◽

Cholesterol Transport ◽

Macrophage Cholesterol Efflux

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [3H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassettea1. Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.

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Naturally occurring and bioengineered apoA-I mutations that inhibit the conversion of discoidal to spherical HDL: the abnormal HDL phenotypes can be corrected by treatment with LCAT

Biochemical Journal ◽

10.1042/bj20070296 ◽

2007 ◽

Vol 406 (1) ◽

pp. 167-174 ◽

Cited By ~ 22

Author(s):

Georgios Koukos ◽

Angeliki Chroni ◽

Adelina Duka ◽

Dimitris Kardassis ◽

Vassilis I. Zannis

Keyword(s):

Gene Transfer ◽

Plasma Cholesterol ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Spherical Particles ◽

Simultaneous Treatment ◽

Cholesterol Ratio ◽

Cholesterol Levels ◽

Atp Binding Cassette Transporter

In the present study we have used adenovirus-mediated gene transfer of apoA-I (apolipoprotein A-I) mutants in apoA-I−/− mice to investigate how structural mutations in apoA-I affect the biogenesis and the plasma levels of HDL (high-density lipoprotein). The natural mutants apoA-I(R151C)Paris, apoA-I(R160L)Oslo and the bioengineered mutant apoA-I(R149A) were secreted efficiently from cells in culture. Their capacity to activate LCAT (lecithin:cholesterol acyltransferase) in vitro was greatly reduced, and their ability to promote ABCA1 (ATP-binding cassette transporter A1)-mediated cholesterol efflux was similar to that of WT (wild-type) apoA-I. Gene transfer of the three mutants in apoA-I−/− mice generated aberrant HDL phenotypes. The total plasma cholesterol of mice expressing the apoA-I(R160L)Oslo, apoA-I(R149A) and apoA-I(R151C)Paris mutants was reduced by 78, 59 and 61% and the apoA-I levels were reduced by 68, 64 and 55% respectively, as compared with mice expressing the WT apoA-I. The CE (cholesteryl ester)/TC (total cholesterol) ratio of HDL was decreased and the apoA-I was distributed in the HDL3 region. apoA-I(R160L)Oslo and apoA-I(R149A) promoted the formation of preβ1 and α4-HDL subpopulations and gave a mixture of discoidal and spherical particles. apoA-I(R151C)Paris generated subpopulations of different sizes that migrate between preβ and α-HDL and formed mostly spherical and a few discoidal particles. Simultaneous treatment of mice with adenovirus expressing any of the three mutants and human LCAT normalized plasma apoA-I, HDL cholesterol levels and the CE/TC ratio. It also led to the formation of spherical HDL particles consisting mostly of α-HDL subpopulations of larger size. The correction of the aberrant HDL phenotypes by treatment with LCAT suggests a potential therapeutic intervention for HDL abnormalities that result from specific mutations in apoA-I.

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Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v971277 ◽

1998 ◽

Vol 9 (7) ◽

pp. 1277-1284 ◽

Cited By ~ 1

Author(s):

T Shoji ◽

Y Nishizawa ◽

T Kawagishi ◽

K Kawasaki ◽

H Taniwaki ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Aortic Pulse Wave Velocity ◽

Hemodialysis Patients ◽

Plasma Lipoproteins ◽

Aortic Atherosclerosis ◽

Intermediate Density Lipoprotein ◽

Control Subjects ◽

Intermediate Density

Patients with chronic renal failure often show accumulation of intermediate-density lipoprotein (IDL). Because recent studies have emphasized the atherogenicity of IDL in the general population, we evaluated the relationship between this lipoprotein and aortic atherosclerosis in uremic patients treated with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL. Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay. Aortic PWV was significantly higher in the hemodialysis patients than in the control subjects. The hemodialysis group showed a significant increase in VLDL and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the control levels. Lp(a) levels did not differ between the two groups. In the hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not. Multiple regression analyses indicated that plasma triglycerides, independent of HDL cholesterol, had a significant association with aortic PWV in the hemodialysis patients but not in the control subjects. Further analyses revealed that aortic PWV in the hemodialysis patients had a significant and independent association with IDL cholesterol, whereas aortic PWV in the control subjects had significant and independent associations with HDL cholesterol and Lp(a). These results demonstrate that IDL is the lipoprotein fraction most closely associated with aortic PWV in the hemodialysis patients.

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