Lipoxins, Resolvins, Protectins, Maresins, and Nitrolipids: Connecting Lipids, Inflammation, and Cardiovascular Disease Risk

Abstract

Essential fatty acids and their metabolites (γ-linolenic acid [GLA], dihomo-GLA, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; prostaglandin E 1 ; prostacyclin [PGI 2 ]; PGI 3 ; lipoxins; resolvins; protectins; maresins; and nitrolipids) prevent platelet aggregation, produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, possess peroxisome proliferator-activated receptor-γ ligand activity, and release nitric oxide. Thus, they lower blood pressure, are anti-arrhythmic and antiinflammatory in nature, reduce low-density lipoprotein cholesterol, ameliorate the adverse actions of homocysteine, activate telomerase, and have cytoprotective propertiesactions that prevent atherosclerosis and cardiovascular disease. Because coronary heart disease (CHD) and atherosclerosis are low-grade systemic inflammatory conditions, it is likely that reduced formation of lipoxins, resolvins, protectins, maresins, and nitrolipids plays a significant role in the pathogenesis of CHD. Hence, development of stable synthetic analogues of lipoxins, resolvins, protectins, and maresins may form a new therapeutic approach to CHD and other low-grade systemic inflammatory conditions.

Peroxisomes, oxidative stress, and inflammation

“…Myelin, the insulating layer of nerve sheaths, contains plasmalogens; absence of the ether phospholipid is associated with progressive neurological impairment [9] . Docosahexaenoic acids, peroxisomally produced omega-3 fatty acids, are the pivotal precursors of resolvins ("resolution-phase interaction products"), maresins ("macrophage mediator in resolving inflammation"), and protectins (formerly called "neuroprotectins") [10][11][12] . These molecules possess potent anti-inflammatory, inflammatory resolving, and immunoregulatory activities.…”

Exercise Is Beneficial: But How and Why?

“…22 In contrast, LXA4 suppresses the production of pro-inflammatory cytokines, IL-6 and TNF-α. 18, 19 These results are in favor of the proposal that anti-inflammatory cytokines, IL-4 and IL-10, induce the expression and synthesis of anti-inflammatory lipid mediators, lipoxins, resolvins, protectins and maresins in addition to their ability to suppress the production of pro-inflammatory cytokines such as IL-2, IL-6, TNF-α, macrophage migration inhibitory factor and high-mobility group box 1 and leukotrienes (LTs).…”

“…17 LXA4 is a potent anti-inflammatory molecule that inhibits leukocyte activation, prevents platelet aggregation, and augments eNO generation and thus can prevent, inhibit and/or reverse atherosclerosis. [18][19][20] There is reasonable evidence to suggest that LXA4 might prevent cardiac arrhythmias. 21 In this context, it is interesting to note that anti-inflammatory cytokines, IL-4 and IL-10, trigger the conversion of AA, EPA and DHA to lipoxins, resolvins, protectins and maresins, suggesting a mechanism by which they are able to suppress inflammation.…”

Beneficial Effects of Eicosapentaenoic Acid in Coronary Heart Disease With Peripheral Vascular Diseases: But How and Why?

“…5 Hence, it is important to measure plasma levels of AA, EPA, DHA, LXs, resolvins, protectins, nitrolipids and EFOX in subjects who are on EPA/DHA and correlate their levels to the degree of atherosclerosis, and as predictors and prognostic markers of CHD. 6 It is worthwhile to study whether oral supplementation of AA, along with EPA/DHA, augments the beneficial actions of ω-PUFAs. Those who respond inadequately to drugs and EPA/DHA may form significantly lesser amounts of LXs resolvins, protectins, nitrolipids and EFOX.…”