Reduced proteoglycan binding of low density lipoproteins from monkeys (Macaca fascicularis) fed a fish oil versus lard diet.

Edwards, Iris J.; Gebre, Abraham K.; Parks, John S.

doi:10.1161/01.atv.11.6.1778

Cited by 19 publications

(7 citation statements)

References 42 publications

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“…These results indicate that SOAT2-derived CE containing monounsaturated FAs in the core of LDL may result in a prolonged residence time of LDL in the artery wall that could lead to accelerated development of atherosclerosis. These fi ndings are in agreement with previous studies showing that dietary consumption of n-3 PUFAs by nonhuman primates resulted in the production of LDL particles with a decreased affi nity for proteoglycans compared with their lard-fed counterparts (32)(33)(34). This study also helps address a number of paradoxical questions that remain unanswered as to what factors appear to be more important in the development of atherosclerosis.…”

Section: Discussionsupporting

confidence: 93%

LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis

Melchior

Sawyer

Kelley

et al. 2013

Journal of Lipid Research

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the pathophysiology of atherosclerosis ( 2 ). After LDL particles enter the intima of the artery wall, they can interact with proteoglycans, which are structural proteins residing in the extracellular matrix that consist of one or more glycosaminoglycan (GAG) side-chains attached to core proteins. The LDL-proteoglycan complex is generally regarded as an electrostatic interaction ( 3 ). The sulfation pattern of the acidic sugar groups that form the GAG chains on the proteoglycans results in an overall negative charge that can interact with clusters of positively charged amino acid residues on apoB-100, the primary apolipoprotein present on the LDL particle ( 4 ). A proteoglycan frequently deposited in atherosclerotic plaques of humans ( 5, 6 ) and mice is biglycan (BGN) ( 7 ).While plasma LDL cholesterol concentrations are predictive of the extent of atherosclerosis, LDL particles are heterogeneous in size and composition, and this heterogeneity may provide additional useful information about the role of LDL in atherosclerosis. For instance, studies have shown that diet-induced alterations in the FA composition of LDL core cholesteryl esters (CEs) can infl uence the atherogenic potential of LDL particles ( 8-11 ). In nonhuman primates, consumption of dietary MUFAs resulted in LDL particles containing a CE core enriched in cholesterol oleate (CO), which were positively associated with coronary artery atherosclerosis ( r = 0.8) ( 10, 11 ). Importantly, a similar diet-related shift in the CE FA composition of LDL has been observed in humans in which consumption of oleate-enriched diets resulted in elevations in the percentage of CO in the LDL CE ( 12 ). Additionally, the large Atherosclerosis Risk in Communities Study revealed a Abstract Several studies in humans and animals suggest that LDL particle core enrichment in cholesteryl oleate (CO) is associated with increased atherosclerosis. Diet enrichment with MUFAs enhances LDL CO content. Steroyl O -acyltransferase 2 (SOAT2) is the enzyme that catalyzes the synthesis of much of the CO found in LDL, and gene deletion of SOAT2 minimizes CO in LDL and protects against atherosclerosis. The purpose of this study was to test the hypothesis that the increased atherosclerosis associated with LDL core enrichment in CO results from an increased affi nity of the LDL particle for arterial proteoglycans. ApoB-100-only Ldlr − /− mice with and without Soat2 gene deletions were fed diets enriched in either cis -MUFA or n-3 PUFA, and LDL particles were isolated. LDL:proteogylcan binding was measured using surface plasmon resonance. Particles with higher CO content consistently bound with higher affi nity to human biglycan and the amount of binding was shown to be proportional to the extent of atherosclerosis of the LDL donor mice. The data strongly support the thesis that atherosclerosis was induced through enhanced proteoglycan binding of LDL resulting from LDL core CO

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Section: Discussionsupporting

confidence: 93%

LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis

Melchior

Sawyer

Kelley

et al. 2013

Journal of Lipid Research

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“…The amount of biglycan binding was also shown to be proportional to the development of atherosclerosis in the apoB-100-only Ldlr -/- mice. Similar results to those of Melchior et al have also been seen in other rodent and primate models, which have repeatedly demonstrated that consumption of MUFAs and SFA, as opposed to n-3 or n-6 PUFA, results in the production of LDL particles with an increased affinity for proteoglycans 17, 27, 28 . These animal trials showed associations between the content of cholesteryl oleate in the CE of the LDL particle core with the amount of LDL proteoglycan binding, both of which were also associated with the amount of atherosclerosis present.…”

Section: Discussionsupporting

confidence: 86%

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans

et al. 2015

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Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets; 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p=0.0005 and p=0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p=0.0243) and DHA-enriched high oleic canola oil (p=0.0249), although high-oleic canola oil had the lowest binding at baseline (p=0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.

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“…However, studies in nonhuman primates fed large quantities of fish oil suggest that nҀ3 fatty acid-enriched LDL particles may be less atherogenic than control LDL particles (54 -56). The latter does not appear to be the result of differences in small compared with large LDL (56) but might be the result of the decreased binding of nҀ3 fatty acid-enriched LDL to arterial proteoglycans, as observed in vitro (57).…”

Section: Effects Of N؊3 Fatty Acids On Plasma Lipids and Lipoproteinsmentioning

confidence: 96%

n−3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects

Jung

Torrejón

Tighe

et al. 2008

The American Journal of Clinical Nutrition

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Dietary nҀ3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid, are important nutrients through the life cycle. Evidence from observational, clinical, animal, and in vitro studies indicates a beneficial role of nҀ3 fatty acids in the prevention and management of cardiovascular disease. Although the precise mechanisms are still unclear, clinical and preclinical studies indicate that the cardioprotective effects of nҀ3 fatty acids may be attributed to a number of distinct biological effects on lipid and lipoprotein metabolism, blood pressure, platelet function, arterial cholesterol delivery, vascular function, and inflammatory responses.Am J Clin Nutr 2008;87(suppl):2003S-9S.

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Reduced proteoglycan binding of low density lipoproteins from monkeys (Macaca fascicularis) fed a fish oil versus lard diet.

Cited by 19 publications

References 42 publications

LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis

LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans

n−3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects

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