Dataset Information

The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.

ABSTRACT:

Objective

Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ?-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosis factor alpha (TNF-?) induced inflammatory responses in human vascular endothelial (EC) and smooth muscle cells (VSMC).

Methods

Primary cultures of human saphenous vein EC and VSMC were employed. We tested the naturally occurring MaR1 as modulator of TNF-? effects, with examination of monocyte adhesion, oxidant stress, and intracellular inflammatory signaling pathways.

Results

MaR1 attenuated TNF-? induced monocyte adhesion and reactive oxygen species (ROS) generation in both EC and VSMC, associated with down-regulated expression (cell surface) of the adhesion molecule E-selectin (in EC) and NADPH-oxidases (NOX4, NOX1, NOX2). MaR1 attenuated TNF-? induced release of pro-inflammatory mediators by EC and VSMC. MaR1 caused an attenuation of TNF-? induced NF-?B activation in both cell types associated with inhibition of I-? Kinase (IKK) phosphorylation, I?B-? degradation and nuclear translocation of the NF- ?B p65 subunit. MaR1 also caused a time-dependent increase in intracellular cyclic AMP (cAMP) in both naive and TNF-? stimulated VSMC and EC.

Conclusions

MaR1 has broad anti-inflammatory actions on EC and VSMC, which may be partly mediated through up-regulation of cAMP and down-regulation of the transcription factor NF-?B. The results suggest that the pro-resolving lipid mediator MaR1 exerts homeostatic actions on vascular cells that counteract pro-inflammatory signals. These findings may have direct relevance for acute and chronic states of vascular inflammation.

SUBMITTER: Chatterjee A

PROVIDER: S-EPMC4237455 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.

Chatterjee Anuran A Sharma Anjali A Chen Mian M Toy Robert R Mottola Giorgio G Conte Michael S MS

PloS one 20141119 11

<h4>Objective</h4>Inflammation and its resolution are central to vascular injury and repair. Maresins comprise a new family of bioactive lipid mediators synthesized from docosahexaenoic acid, an ω-3 polyunsaturated fatty acid. They have been found to exert anti-inflammatory and pro-resolving responses in macrophages, neutrophils and bronchial epithelial cells and impart beneficial actions in murine models of peritonitis and colitis. We investigated the impact of maresin-1 (MaR1) on tumor necrosi ...[more]

PMID: 25409514

Similar Datasets

Project description:Essentials Specialized proresolving mediators (SPMs) promote the resolution of inflammation. This study sought to investigate the effects of SPMs on human platelet function. The SPM, Maresin 1, enhanced hemostatic, but suppressed inflammatory functions of platelets. SPMs uniquely regulate platelet function and may represent a new class of antiplatelet agents.SummaryBackground Antiplatelet therapy is a cornerstone of modern medical practice and is routinely employed to reduce the likelihood of myocardial infarction, thrombosis and stroke. However, current antiplatelet therapies, such as aspirin, often have adverse side-effects, including increased risk of bleeding, and some patients are relatively 'aspirin-resistant'. Platelets are intimately involved in hemostasis and inflammation, and clinical consequences are associated with excessive or insufficient platelet activation. Objectives A major unmet need in the field of hematology is the development of new agents that safely prevent unwanted platelet activation in patients with underlying cardiovascular disease, while minimizing the risk of bleeding. Here, we investigate the potential of endogenously produced, specialized pro-resolving mediators (SPMs) as novel antiplatelet agents. SPMs are a recently discovered class of lipid-derived molecules that drive the resolution of inflammation without being overtly immunosuppressive. Methods Human platelets were treated with lipoxin A4, resolvin D1, resolvin D2, 17-HDHA or maresin 1 for 15 min, then were subjected to platelet function tests, including spreading, aggregation and inflammatory mediator release. Results We show for the first time that human platelets express the SPM receptors, GPR32 and ALX. Furthermore, our data demonstrate that maresin 1 differentially regulates platelet hemostatic function by enhancing platelet aggregation and spreading, while suppressing release of proinflammatory and prothrombotic mediators. Conclusions These data support the concept that SPMs differentially regulate platelet function and may represent a novel class of antiplatelet agents. SPMs also may play an important role in the resolution of inflammation in cardiovascular diseases.

Dataset Information

The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.

Objective

Methods

Results

Conclusions

Publications

The pro-resolving lipid mediator maresin 1 (MaR1) attenuates inflammatory signaling pathways in vascular smooth muscle and endothelial cells.

Similar Datasets

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