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Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice.

ABSTRACT: INTRODUCTION:The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. OBJECTIVE:We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. METHODS:Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. RESULTS:Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. CONCLUSION:This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection.

SUBMITTER: Forrest LM

PROVIDER: S-EPMC3258669 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice.

Forrest Lolita M LM Boudyguina Elena E Wilson Martha D MD Parks John S JS

Atherosclerosis 20111029 1

<h4>Introduction</h4>The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides.<h4>Objective</h4>We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis.<h4>Methods</h4>Mice were fed palm, ...[more]

PMID: 22100249

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Project description:ObjectiveSalsalate is a prodrug of salicylate that lowers blood glucose in people with type 2 diabetes. AMP-activated protein kinase (AMPK) is an αβγ heterotrimer which inhibits macrophage inflammation and the synthesis of fatty acids and cholesterol in the liver through phosphorylation of acetyl-CoA carboxylase (ACC) and HMG-CoA reductase (HMGCR), respectively. Salicylate binds to and activates AMPKβ1-containing heterotrimers that are highly expressed in both macrophages and liver, but the potential importance of AMPK and ability of salsalate to reduce atherosclerosis have not been evaluated.MethodsApoE-/- and LDLr-/- mice with or without (-/-) germline or bone marrow AMPKβ1, respectively, were treated with salsalate, and atherosclerotic plaque size was evaluated in serial sections of the aortic root. Studies examining the effects of salicylate on markers of inflammation, fatty acid and cholesterol synthesis and proliferation were conducted in bone marrow-derived macrophages (BMDMs) from wild-type mice or mice lacking AMPKβ1 or the key AMPK-inhibitory phosphorylation sites on ACC (ACC knock-in (KI)-ACC KI) or HMGCR (HMGCR-KI).ResultsSalsalate reduced atherosclerotic plaques in the aortic roots of ApoE-/- mice, but not ApoE-/- AMPKβ1-/- mice. Similarly, salsalate reduced atherosclerosis in LDLr-/- mice receiving wild-type but not AMPKβ1-/- bone marrow. Reductions in atherosclerosis by salsalate were associated with reduced macrophage proliferation, reduced plaque lipid content and reduced serum cholesterol. In BMDMs, this suppression of proliferation by salicylate required phosphorylation of HMGCR and the suppression of cholesterol synthesis.ConclusionsThese data indicate that salsalate suppresses macrophage proliferation and atherosclerosis through an AMPKβ1-dependent pathway, which may involve HMGCR phosphorylation and cholesterol synthesis. Since rapidly-proliferating macrophages are a hallmark of atherosclerosis, these data indicate further evaluation of salsalate as a potential therapeutic agent for treating atherosclerotic cardiovascular disease.

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Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice.

Publications

Echium oil reduces atherosclerosis in apoB100-only LDLrKO mice.

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