Regression of pre-established atherosclerosis in the apoE−/− mouse by conjugated linoleic acid

Toomey, Sinéad; Roche, Helen M.; Fitzgerald, D; Belton, Orina

doi:10.1042/bst0311075

Cited by 70 publications

(40 citation statements)

References 52 publications

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“…Studies in cell cultures have demonstrated protective properties (8,11,15,38). In animals, these properties can be observed while using either the CLA isomeric mixture (cis-9,trans-11-and trans-10,cis-12-CLA, 50:50) (17,37) or selected CLA isomers (cis-9,trans-11-or trans-10,cis-12-CLA) (16,32). In most studies, these fatty acids consistently attenuate the formation of primary vascular lesions (fatty streaks) or induce regression of preestablished lesions (16,17).…”

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confidence: 99%

“…Although present in minor amounts in diets, CLA has been receiving growing interest for its multiple health-related effects reported in various animal models (35). Especially, the antiatherogenic properties of CLA are now supported by many animal studies in rabbits (16), mice (32), and hamsters (37). Studies in cell cultures have demonstrated protective properties (8,11,15,38).…”

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confidence: 99%

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Acis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster

Valeille¹,

Férézou²,

Amsler³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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in several animal models, including hamsters, but the mechanism of action of the main food-derived CLA isomer is unknown in this species. This study thus focused on cis-9,trans-11-CLA (rumenic acid), and its effect was compared with that of fish oil, which is known to influence several aspects of atherogenesis. Syrian hamsters were fed (for 12 wk) diets containing 20% (wt/wt) butter fat (B diet) or the same diet augmented with either 1% (wt/wt) of a cis-9,trans-11-CLArich oil (BR diet) or 1% (wt/wt) fish oil (BF diet). The BR diet induced the lowest aortic lipid deposition (from Ϫ30% to Ϫ45%) among the butter oil-fed hamsters. In this group, plasma also displayed a reduced non-HDL-to-HDL-cholesterol ratio (21% less than in the butter oil group) and inflammatory serum amyloid A levels (70 -80%) and an improvement of anti-oxidized LDL paraoxonase activity (all P Ͻ 0.05). Compared with the B group, the beneficial effects of the BR diet could be further explained in part by preventing the high VCAM-1 expression rate, increasing (30%) ATP-binding cassette subfamily A1 expression in the aorta, and downregulating expression of inflammatory-related genes (TNF-␣, IL-1␤, and cyclooxygenase 2, 2-to 2.8-fold, P Ͻ 0.05). This effect was partly associated with an activation of peroxisome proliferator-activating receptor (PPAR)/liver X receptor (LXR)-␣ signaling cascade. Interestingly, activation of PPAR/LXR-␣ signaling was not observed in hamsters fed the BF diet, in which the early signs of atherogenesis were increased. In conclusion, this study demonstrated that milk fat-rich cis-9,trans-11-CLA reduces the atherogenic process in hyperlipidemic hamsters.

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confidence: 99%

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confidence: 99%

Acis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster

Valeille¹,

Férézou²,

Amsler³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…The doses used in our studies were based on previous published works. 19,20 Urine was collected overnight in metabolic cages; blood samples were obtained by retro-orbital bleeding from animals fasted overnight, as previously described. 9,10 …”

Section: Animals and Experimental Protocolsmentioning

confidence: 99%

Thromboxane receptor blockade improves the antiatherogenic effect of thromboxane A2 suppression in LDLR KO mice

Cyrus

Yao

Ding

et al. 2006

Blood

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Suppression of thromboxane (Tx)A IntroductionAtherosclerosis is a complex and chronic inflammatory disease of the arterial wall influenced by diverse biochemical factors, including cytokines, chemokines, and growth factors. 1 One group of these mediators is represented by the prostanoids, a large family of bioactive lipids generating from arachidonic acid by the enzyme cyclooxygenase (COX). 2 The biosynthesis of prostanoids, specifically thromboxane A 2 (TxA 2 ) and prostacyclin (PGI 2 ), is grossly altered in human as well as in experimental atherosclerosis. 3,4 The increase in PGI 2 reflects in part the induction of both COX isoforms, COX-1 and COX-2, in the arterial wall. 5 However, most of the TxA 2 in this clinical setting derives from platelet COX-1 activation. 6 Both compounds may influence atherogenesis in different ways by modulating vascular inflammatory responses, cell growth, apoptosis, migration, and proliferation, processes that have all been implicated in atherosclerosis. 7 Cardioprotection from aspirin is widely attributed to its inhibitory effect on platelet COX-1-dependent TxA 2 formation. 8 Previously, we have provided evidence for the importance of COX-1-dependent TxA 2 formation in atherogenesis. Thus, targeted pharmacological inhibition of COX-1 by indomethacin as well as low-dose aspirin, but not COX-2 by nimesulide, retards atherogenesis in low-density lipoprotein receptor-deficient (LDLR KO) mice. 9-11 Consistent with our observation, selective inhibition of COX-1 enzyme activity and genetic deletion of COX-1 gene expression both reduce atherogenesis in another mouse model, the apolipoprotein E-KO (apoE-KO). 12,13 However, challenging this view, a recent report showed that COX-1 deficiency in bone marrow-derived cells worsens early atherosclerosis. 14 In general, although inhibition of COX-1 activity suppresses TxA 2 biosynthesis, it does not prevent the formation and, most importantly, the actions of other eicosanoids, such as hydroxyeicosatetraenoic acids and isoprostanes, which can both directly stimulate the receptor for TxA 2 and trigger proinflammatory reactions. 15 Interestingly, antagonism or genetic deletion of the TxA 2 receptor, called TP, reduces atherosclerosis in apoE-KO mice. 16,17 Taken together, the data would support the hypothesis that suppression of TxA 2 formation alone would not afford the most antiatherogenic effect because of the coincidental presence of nonconventional TP ligands, which could still favor a proinflammatory and proatherogenic vascular phenotype. Therefore, antagonism of the TP receptor associated with suppression of TxA 2 biosynthesis could augment the beneficial anti-inflammatory effects of COX-1 inhibition and be a more effective therapeutic approach to modulate atherogenesis than suppression of COX-1 activation alone.To this end, we treated LDLR KO mice with SC-560, a selective COX-1 inhibitor, 18 BM-573, a TP antagonist, 19 or a combination of the 2 drugs for 12 weeks during the development of atherogenesis. At the end of the treatments, we fou...

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“…It has been shown to exhibit in animal studies beneficial health effects on cancer prevention and treatment, and cardiovascular risk (reviewed by Wahle et al (2004)). Chemically synthesised CLA (cis-9, trans-11 CLA or mixture of cis-9, trans-11 þ trans-10, cis-12 CLA) have been shown to protect against the development and progression of atherosclerosis in rabbits (Kritchevsky et al, 2002 and2004), hamsters (Nicolosi et al, 1997;Wilson et al, 2000) and ApoE-KO mice (Toomey et al, 2003) when a pro-atherogenic diet was fed. Moreover, the addition of a cis-9, trans-11 CLA-rich mixture to butter depressed some risk factors of CVD in cholesterol-fed hamsters (Valeille et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Butters rich either in trans-10-C18:1 or in trans-11-C18:1 plus cis-9, trans-11 CLA differentially affect plasma lipids and aortic fatty streak in experimental atherosclerosis in rabbits

Roy

Chardigny

Bauchart

et al. 2007

Animal

113

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Dairy fat contains high amounts of saturated fatty acids (FA), which are associated with cardiovascular disease (CVD) risk. Manipulation of dairy cows nutrition allows to decrease the saturated FA content of milk fat, and is associated with increases either in conjugated linoleic acid (CLA) and trans-11-C18:1 contents, or in trans-10-C18:1 content. CLA putatively exhibits beneficial properties on CVD risk, whereas trans FA are suspected to be detrimental. The present study compared the effects of a trans-10-C18:1-rich butter (T10 butter), a trans-11-C18:1 þ CLA-rich butter (T11-CLA butter) and a standard butter (S butter) on lipid parameters linked to the CVD risk and fatty streaks. Thirty-six White New Zealand rabbits were fed one of the three butters (12% of the diet, plus 0.2% cholesterol) for 6 (experiment 1) or 12 (experiment 2) weeks. Liver lipids, plasma lipids and lipoprotein concentrations (experiments 1 and 2) and aortic lipid deposition (experiment 2) were determined. The T10 butter increased VLDL-cholesterol compared with the two others, and total and LDL-cholesterol compared with the T11-CLA butter ( P , 0.05). The T10 butter also increased non-HDL/HDL ratio and aortic lipid deposition compared with the T11-CLA butter ( P , 0.05). The T11-CLA butter non-significantly reduced aortic lipid deposition compared with the S butter, and decreased HDLcholesterol and increased liver triacyglycerols compared with the two other butters ( P , 0.05). These results suggest that, compared with the S butter, the T10 butter had detrimental effects on plasma lipid and lipoprotein metabolism in rabbits, whereas the T11-CLA butter was neutral or tended to reduce the aortic lipid deposition.

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Regression of pre-established atherosclerosis in the apoE−/− mouse by conjugated linoleic acid

Cited by 70 publications

References 52 publications

Acis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster

Acis-9,trans-11-conjugated linoleic acid-rich oil reduces the outcome of atherogenic process in hyperlipidemic hamster

Thromboxane receptor blockade improves the antiatherogenic effect of thromboxane A2 suppression in LDLR KO mice

Butters rich either in trans-10-C18:1 or in trans-11-C18:1 plus cis-9, trans-11 CLA differentially affect plasma lipids and aortic fatty streak in experimental atherosclerosis in rabbits

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