Resolving Lipid Mediators Maresin 1 and Resolvin D2 Prevent Atheroprogression in Mice.
Circ Res
; 119(9): 1030-1038, 2016 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-27531933
ABSTRACT
RATIONALE Atheroprogression is a consequence of nonresolved inflammation, and currently a comprehensive overview of the mechanisms preventing resolution is missing. However, in acute inflammation, resolution is known to be orchestrated by a switch from inflammatory to resolving lipid mediators. Therefore, we hypothesized that lesional lipid mediator imbalance favors atheroprogression. OBJECTIVE:
To understand the lipid mediator balance during atheroprogression and to establish an interventional strategy based on the delivery of resolving lipid mediators. METHODS ANDRESULTS:
Aortic lipid mediator profiling of aortas from Apoe-/- mice fed a high-fat diet for 4 weeks, 8 weeks, or 4 months revealed an expansion of inflammatory lipid mediators, Leukotriene B4 and Prostaglandin E2, and a concomitant decrease of resolving lipid mediators, Resolvin D2 (RvD2) and Maresin 1 (MaR1), during advanced atherosclerosis. Functionally, aortic Leukotriene B4 and Prostaglandin E2 levels correlated with traits of plaque instability, whereas RvD2 and MaR1 levels correlated with the signs of plaque stability. In a therapeutic context, repetitive RvD2 and MaR1 delivery prevented atheroprogression as characterized by halted expansion of the necrotic core and accumulation of macrophages along with increased fibrous cap thickness and smooth muscle cell numbers. Mechanistically, RvD2 and MaR1 induced a shift in macrophage profile toward a reparative phenotype, which secondarily stimulated collagen synthesis in smooth muscle cells.CONCLUSIONS:
We present evidence for the imbalance between inflammatory and resolving lipid mediators during atheroprogression. Delivery of RvD2 and MaR1 successfully prevented atheroprogression, suggesting that resolving lipid mediators potentially represent an innovative strategy to resolve arterial inflammation.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Docosa-Hexaenoicos
/
Mediadores da Inflamação
/
Aterosclerose
/
Metabolismo dos Lipídeos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2016
Tipo de documento:
Article