Specialized pro-resolving mediators in cardiovascular diseases

Abstract

The resolution of inflammation is a highly regulated process enacted by endogenous mediators including specialized pro-resolving lipid mediators (SPMs): the lipoxins, resolvins, protectins and maresins. SPMs activate specific cellular receptors to temper the production of pro-inflammatory mediators, diminish the recruitment of neutrophils, and promote the clearance of dead cells by macrophages. These mediators also enhance host-defense and couple resolution of inflammation to subsequent phases of tissue repair. Given that unresolved inflammation plays a causal role in the development of cardiovascular diseases, an understanding of these endogenous pro-resolving processes is critical for determining why cardiovascular inflammation does not resolve. Here, we discuss the receptor-dependent actions of resolvins and related pro-resolving mediators and highlight their emerging roles in the cardiovascular system. We propose that stimulating resolution could be a novel approach for treating chronic cardiovascular inflammation without promoting immunosuppression.

Resolution of vascular injury: Specialized lipid mediators and their evolving therapeutic implications

“…However, the same transgenic mice fed a high-cholesterol diet developed more significant atherosclerosis compared to wild type controls (Merched, Serhan et al 2011). The reason for this is rooted in the fact that 15-LOX can also contribute to oxidation of low-density lipoprotein (Fredman and Spite 2017). In this scenario, diet composition determined the preferred pathway through which fatty acids were metabolized, leading to either SPM production or the alternative formation of pro-atherogenic lipids.…”

The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke

“…D-series resolvins, through the DRV1/GPR32 receptor, also regulate the functioning of the immune system, preventing the differentiation of T-lymphocytes towards Th1 and Th12, and promoting regulatory cell (Tr) formation [ 47 , 48 ]. It has been proven that the atherosclerotic process features the transformation of vascular smooth muscle cells (SMCs) into a proliferative and migratory phenotype [ 49 ]. As a result, SMCs migrate to the site that was altered by atherosclerosis and stabilise the atherosclerotic plaque, forming its main constituent.…”

Aneurysmal Subarachnoid Hemorrhage and Resolution of Inflammation

“…Atherosclerotic plaques readily incorporate omega-3 FAs, and a higher plaque EPA content is associated with a reduced number of foam cells and macrophages, as well as increased plaque stability, as determined by a well-formed fibrous cap [80]. Additionally, signs of defective resolution of inflammation have been identified in atherosclerotic plaques [81]. One major function of SPMs (particularly maresins) is to induce phenotypic conversion of macrophages, which decrease inflammation and promote tissue regeneration [16].…”

“…One major function of SPMs (particularly maresins) is to induce phenotypic conversion of macrophages, which decrease inflammation and promote tissue regeneration [16]. In animal models of atherosclerosis, a traditional Western high-fat diet disrupts the homeostasis of inflammation resolution by nutrigenetic modulation of the 12/15-LOX pathways, thereby inhibiting the generation of protective SPMs [81,82]. These recent findings in atherosclerosis, particularly the involvement of docosanoids in vascular inflammation, provide biological plausibility that defective resolution of inflammation is implicated in the pathogenesis of IA growth and rupture.…”