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Lipid preresolution mediators: their therapeutic potential in atherosclerosis

Publication at First Faculty of Medicine |
2019

Abstract

The resolution of acute inflammation is an active process necessary to tissue repair, regeneration and maintenance of homeostasis. Biologically active derivatives of polyunsaturated fatty acids, referred to as lipid or specialized pro-resolving mediators (SPM), play an important role in the resolution of acute inflammation.

Based on stereospecific analysis, four groups of these compounds are identified, namely lipoxins, resolvins, protectins, and maresins. Pro-resolving mediators are characterized by a broad spectrum of effects: they inhibit the production of pro-inflammatory cytokines, inhibit recruitment of PMN to injured tissues, and stimulate macrophages to epherocytosis (i.e. the clearance of apoptotic PMN).

These steps are followed by repair and regeneration of inflamed tissue. From the pharmacobiologic point of view is important that the anti-inflammatory and pro-resolution effects of SPM are not associated with immunosuppression.

The absolute or relative deficiency of the pro-resolving mediators may cause the unresolved inflammation and the transition of acute inflammation to chronic form. Low-grade, unresolved inflammation underlies numerous chronic diseases and conditions such as atherosclerosis, obesity, diabetes mellitus type 2 and their clinical complications.

It is currently under investigation to what extent atherosclerosis can be favorably influenced by lipid pro-resolving mediators. Results of experimental studies in animal models revealed that SPM attenuated the progression of vascular lesions and stabilize vulnerable atherosclerotic plaques.

In patients with advanced atherosclerosis, low to immeasurable plasma concentrations of some lipid pro-resolving mediators, mainly resolvins of the D series, have been reported. The local formation of these mediators and their blood concentrations increase significantly during the dietary supplementation of polyunsaturated fatty acids of the n-3 series.