Omega-3 Fatty Acids Ameliorate Atherosclerosis by Favorably Altering Monocyte Subsets and Limiting Monocyte Recruitment to Aortic Lesions

Abstract

Objective Fish oil (FO), containing n-3 fatty acids (FAs), attenuates atherosclerosis. We hypothesized that n-3 FA-enriched oils are atheroprotective through alteration of monocyte subsets and their trafficking into atherosclerotic lesions. Methods and Results Low density lipoprotein receptor knockout (LDLr−/−) and apolipoprotein E−/− (apoE) mice were fed diets containing 10% (calories) as palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% PO, echium oil (EO; containing 18:4 n-3) or FO. Compared to PO-fed LDLr−/− mice, EO and FO significantly reduced plasma cholesterol, splenic Ly6Chi monocytosis by ~50%, atherosclerosis by 40–70%, monocyte trafficking into the aortic root by ~50%, and atherosclerotic lesion macrophage content by 30–44%. In contrast, atherosclerosis and monocyte trafficking into the artery wall was not altered by n-3 FAs in apoE−/− mice; however, Ly6Chi splenic monocytes positively correlated with aortic root intimal area across all diet groups. In apoE−/− mice, FO reduced the percentage of blood Ly6Chi monocytes, despite an average two-fold higher plasma cholesterol relative to PO. Conclusions The presence of splenic Ly6Chi monocytes parallels the appearance of atherosclerotic disease in both LDLr−/− and apoE−/− mice. Furthermore, n-3 FAs favorably alter monocyte subsets independently from effects on plasma cholesterol, and reduce monocyte recruitment into atherosclerotic lesions.

In vivo activation of leukocyte GPR120/FFAR4 by PUFAs has minimal impact on atherosclerosis in LDL receptor knockout mice

“…The PCR products were separated on 0.8% agarose gels and visualized with ethidium bromide. A series of male and female genomic DNA mixtures The n-3 PUFAs as well as the n-6 PUFAs are atheroprotective in mice, nonhuman primates, and humans (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In humans, dietary n-3 PUFAs, EPA (20:5 n-3), and DHA (22:6 n-3) found in fish oil (FO) are anti-inflammatory and lower plasma TG, but not plasma LDL cholesterol, a primary risk factor for atherosclerosis in humans (20,21).…”

“…Monocyte recruitment was evaluated as reported previously (18). Briefly, aortic root sections were taken as described below and the number of beads per section in atherosclerotic lesions was counted manually at 20× magnification.…”

“…Aortic root cross-sections and liver sections were fixed and incubated with anti-CD68 antibody (AbDSerotec; clone FA11), antiCD11c antibody (BD Pharmingen; clone HL3), or anti-cleaved caspase-3 antibody (Abcam; polyclonal #ab2302) (1:200, overnight) and quantified as described previously (18).…”

Microalgal Oil Supplementation Has an Anti-Obesity Effect in C57BL/6J Mice Fed a High Fat Diet

“…Many studies have demonstrated protective effects of omega-3s against cardiovascular disease (1), cancer (2), atherosclerosis (3), and obesity (4). However, the omega-6/omega-3 ratio plays a critical role in the outcome; high amounts of omega-6 fatty acids have been shown to be associated with several diseases such as cardiovascular disease, cancer, inflammatory disease, and autoimmune disorders, while higher levels of omega-3 averts such negative effects (5).…”

Dietary Docosahexaenoic Acid Reduces Oscillatory Wall Shear Stress, Atherosclerosis, and Hypertension, Most Likely Mediated via an IL‐1–Mediated Mechanism

“…ALA may have a cardioprotective role; however, the overall evidence is mixed and remains inconclusive 51, 52. Similarly, several animal models of atherosclerosis have investigated the anti‐atherogenic effects of n3FAs,53 but these studies also did not directly define the differential effects of individual n3FAs on atherosclerosis. To our knowledge, this study is the first to define a common anti‐atherogenic and anti‐hypertensive mechanism of DHA.…”