Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis

Borow, Kenneth M.; Nelson, John; Mason, R. Preston

doi:10.1016/j.atherosclerosis.2015.07.035

Cited by 155 publications

(125 citation statements)

References 108 publications

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“…In addition, EPA exerted beneficial effects on the pathophysiologic cascade from onset of plaque formation to rupture by incorporating into membrane phospholipids and atherosclerotic plaques. EPA also improved atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol [50]. Based on the result of Fig.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

Chen

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis. Methods: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively. Results: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group. Conclusions: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

Chen

Zhang

et al. 2018

Cell Physiol Biochem

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“…EPA has favorable effects on various atherogenic parameters including reductions in the plasma levels of triglycerides (TGs), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), remnant-like particle cholesterol (RLP-C), apolipoprotein C-III (apoC-III), and oxidized low-density lipoprotein (ox-LDL) particles [4,5]. Importantly, EPA does not increase LDL-C levels [5].…”

Section: Effects Of Epa On Lipids and Lipoproteinsmentioning

confidence: 99%

“…The evidence supporting beneficial effects of EPA on multiple steps of the atherosclerotic pathway has been reviewed extensively [4,14]. Figure 2 provides an overview of the pleiotropic effects of EPA in the atherosclerotic pathway [15].…”

Section: Pleiotropic Effects Of Epa In the Atherosclerotic Pathwaymentioning

confidence: 99%

“…Anti-inflammatory effects of EPA include beneficial modulation of pro-and anti-inflammatory cytokine levels [23,24] and reduction of high-sensitivity C-reactive protein levels [11]. EPA is a substrate for a class of pro-resolving mediators called resolvins, which promote resolution of vascular inflammation [4,14,25,26]. For example, the EPA-derived resolvin RvE1 has been shown to act on leukocytes to modulate adhesion molecules and to exhibit antiplatelet actions [27].…”

Section: Pleiotropic Effects Of Epa In the Atherosclerotic Pathwaymentioning

confidence: 99%

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Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

Nelson¹,

True

et al. 2017

Postgraduate Medicine

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Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk. ARTICLE HISTORY

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“…A subsequent meta-analysis suggested that beneficial effects of statin therapy in patients with renal dysfunction are significantly related to the level of residual kidney function [16]. Of particular interest was the observation that there was no clear relationship between LDL-C reduction and CV benefit in patients on hemodialysis [16,17]. …”

Section: Unmet Needs With Traditional Approaches To Mitigation Of Carmentioning

confidence: 99%

Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review

Borow¹,

Mason

Vijayaraghavan

2017

Cardiorenal Med

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Background: Patients with end-stage renal disease on hemodialysis have excess cardiovascular disease (CVD) burden with substantially increased CV event rates compared with the general population. Summary: Traditional interventions that, according to standard clinical guidelines, reduce CV risk such as antihypertensive therapy, diet, exercise, and statins are not similarly effective in the hemodialysis population. This raises the question of whether additional risk factors, such as enhanced inflammation and oxidative stress, may drive the increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic plaque as well as membrane phospholipid bilayers and produces beneficial effects on inflammatory and oxidative mechanisms involved in atherosclerotic plaque formation and progression. EPA levels and the ratio of EPA to the omega-6 polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis patients. Serum EPA levels have been inversely correlated with proinflammatory cytokines, and the EPA/AA ratio has been inversely associated with CV events in hemodialysis cohorts. Three recent studies involving over 800 hemodialysis patients and follow-up of 2-3 years suggest that EPA therapy may improve clinical outcomes in this patient population as evidenced by significant reductions in cardiovascular mortality, all-cause mortality, and/or CV events. Key Messages: Further studies with high-purity EPA are warranted in patients on hemodialysis, especially given the fact that other interventions including antihypertensives, diet, exercise, and statins have not provided meaningful benefit.

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Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis

Cited by 155 publications

References 108 publications

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review

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