Classes of Lipid Mediators and Their Effects on Vascular Inflammation in Atherosclerosis

Abstract

It is commonly believed that the inactivation of inflammation is mainly due to the decay or cessation of inducers. In reality, in connection with the development of atherosclerosis, spontaneous decay of inducers is not observed. It is now known that lipid mediators originating from polyunsaturated fatty acids (PUFAs), which are important constituents of all cell membranes, can act in the inflamed tissue and bring it to resolution. In fact, PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are precursors to both pro-inflammatory and anti-inflammatory compounds. In this review, we describe the lipid mediators of vascular inflammation and resolution, and their biochemical activity. In addition, we highlight data from the literature that often show a worsening of atherosclerotic disease in subjects deficient in lipid mediators of inflammation resolution, and we also report on the anti-proteasic and anti-thrombotic properties of these same lipid mediators. It should be noted that despite promising data observed in both animal and in vitro studies, contradictory clinical results have been observed for omega-3 PUFAs. Many further studies will be required in order to clarify the observed conflicts, although lifestyle habits such as smoking or other biochemical factors may often influence the normal synthesis of lipid mediators of inflammation resolution.

Differential effects of plant and animal fats on obesity‐induced dyslipidemia and atherosclerosis in Ldlr−/−.Leiden mice

“…Omega‐3 fatty acid‐derived oxylipins (anti‐inflammatory) were elevated and arachidonic acid (omega‐6) oxylipins (pro‐inflammatory) were reduced 34 which overall was associated with reduced inflammation in these tissues. It is conceivable that similar effects may occur in vascular tissue based on previous reports demonstrating an important role for oxylipins in vascular inflammation 57 . Cholesterol‐independent effects of such mediators on atherosclerosis have also been reported 58 .…”

“…It is conceivable that similar effects may occur in vascular tissue based on previous reports demonstrating an important role for oxylipins in vascular inflammation. 57 Cholesterol-independent effects of such mediators on atherosclerosis have also been reported. 58 Differences in the PUFA content and composition of the experimental diets in the current study may thus have differentially affected the balance of pro-and antiinflammatory oxylipins within the vasculature, contributing to observed differences in atherosclerotic disease development.…”

Lipid-Sensing Receptor FFAR4 Modulates Pulmonary Epithelial Homeostasis following Immunogenic Exposures Independently of the FFAR4 Ligand Docosahexaenoic Acid (DHA)

“…Among these ω-3-PUFAs, studies identify that DHA, in particular, exhibits the broadest anti-inflammatory response via numerous modes of action and thus has strong therapeutic potential in diseases such as those of the lung [ 12 , 13 , 14 ]. DHA is critical to cell membrane integrity and participates in anti-inflammatory signaling through the generation of lipid mediators and through the ligation of lipid-sensing free fatty acid receptor 4 (FFAR4) [ 15 , 16 , 17 , 18 ].…”