Omega-3 fatty acids and leukocyte-endothelium adhesion: Novel anti-atherosclerotic actions

Abstract

Endothelial cells (ECs) play a role in the optimal function of blood vessels. When endothelial function becomes dysregulated, the risk of developing atherosclerosis increases. Specifically, upregulation of adhesion molecule expression on ECs promotes the movement of leukocytes, particularly monocytes, into the vessel wall. Here, monocytes differentiate into macrophages and may become foam cells, contributing to the initiation and progression of an atherosclerotic plaque. The ability of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) to influence the expression of adhesion molecules by ECs and to modulate leukocyte-endothelial adhesion has been studied in cell culture using various types of ECs, in animal feeding studies and in human trials; the latter have tended to evaluate soluble forms of adhesion molecules that circulate in the bloodstream. These studies indicate that n-3 PUFAs (both eicosapentaenoic acid and docosahexaenoic acid) can decrease the expression of key adhesion molecules, such as vascular cell adhesion molecule 1, by ECs and that this results in decreased adhesive interactions between leukocytes and ECs. These findings suggest that n-3 PUFAs may lower leukocyte infiltration into the vascular wall, which could contribute to reduced atherosclerosis and lowered risk of cardiovascular disease.

Activation of GPR81 by lactate inhibits oscillatory shear stress‐induced endothelial inflammation by activating the expression of KLF2

“…Increased expression of adhesion molecules by endothelial cells induces monocytes to roll along and adhere to the endothelial wall. Monocytes then migrate into the vessel wall and differentiate into macrophages, and potentially, foam cells, which triggers the formation of atherosclerotic plaque . Various methods of preventing the expression of cellular adhesion molecules have been proposed, such as RNAi targeting or modulation of specific signaling pathways, such as TLR‐NF‐κB .…”

Lowering the linoleic acid to alpha-linoleic acid ratio decreases the production of inflammatory mediators by cultured human endothelial cells

“…PUFAs including EPA, docosapentaenoic acid (DPA) and DHA, while LA can be converted to AA and beyond [7]. The conversion of ALA into LC n-3 PUFAs may be important for the physiological effects of ALA [7].…”

“…PUFAs including EPA, docosapentaenoic acid (DPA) and DHA, while LA can be converted to AA and beyond [7]. The conversion of ALA into LC n-3 PUFAs may be important for the physiological effects of ALA [7]. Although the conversion efficiency may be limited in humans [8], ALA may constitute an alternative and important source of LC n-3 PUFAs given the greater availability of sources rich in ALA such as walnuts, flaxseed, green leafy vegetables and plant oils including canola and soybean oils [9] compared to marine-derived LC n-3 PUFAs.…”

“…Although the conversion efficiency may be limited in humans [8], ALA may constitute an alternative and important source of LC n-3 PUFAs given the greater availability of sources rich in ALA such as walnuts, flaxseed, green leafy vegetables and plant oils including canola and soybean oils [9] compared to marine-derived LC n-3 PUFAs. Most Western diets contain an excess of LA over ALA [7]. Lowering the ratio of LA to ALA is likely to favour synthesis of EPA [7].…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…Moreover, numerous in vitro and in vivo investigations have shown that omega-3 PUFAs are able to modulate diverse key steps involved in atherosclerotic plaque formation (reviewed in [44]). Specifically, omega-3 PUFAs exert potent anti-inflammatory properties in polarized macrophages [45,46] and are able to inhibit the expression of adhesion molecules by ECs [39,47], thus decreasing leukocyte infiltration into the vascular wall [48]. In ApoE -/mice, omega-3 PUFA treatments significantly attenuated the development and destabilization of atherosclerotic plaques [49].…”