Effects of Pro-Resolving Lipid Mediators on Nitric Oxide and Prostacyclin Pathways in Human Endothelial Cells

Introduction and Aim: Inflammation plays a central role in the development and progression of atherosclerosis. Pro- resolving lipid mediators, including Resolvins (RvE1) and Maresins (MaR1) are key regulators of the resolution phase of inflammation. Despite their known anti-inflammatory effects, their impact on nitric oxide (NO) and prostacyclin (PGI2) levels in human umbilical vein endothelial cells (HUVECs) remains underexplored. This study investigates the effects of RvE1 and MaR1 on vascular inflammation, focusing on NO and PGI2 in HUVECs. Methods: An in vitro inflammatory model was established by incubating HUVECs with lipopolysaccharides (LPS, 100 µg/mL) and interleukin-1 beta (IL-1β, 100 ng/mL) for 24 hours. RvE1 and MaR1 (100 nM) were then applied under the same conditions. Levels of tumor necrosis factor-alpha (TNF-α), total nitrite-nitrate, and the stable PGI2 metabolite 6- keto-PGF1α were measured in the incubation medium using ELISA. Results and Discussion: LPS and IL-1β significantly increased TNF-α levels, confirming the inflammatory response. RvE1 and MaR1 significantly reduced nitrite-nitrate levels, suggesting their role in mitigating vascular inflammation. However, no significant changes were observed in 6-keto-PGF1α levels (n=3-4, p>0.05). These findings highlight the selective effects of RvE1 and MaR1 on different pathways involved in endothelial inflammation. Conclusion: This preliminary study demonstrates that RvE1 and MaR1 appear to reduce nitrite-nitrate levels, their lack of impact on 6-keto-PGF1α suggests distinct pathway-specific actions that warrant further investigation. Future studies with larger sample sizes, varied inflammatory conditions, are essential to confirm these findings and better understand their therapeutic potential. Relevance to AtheroNET: This research aligns with AtheroNET's goal of exploring novel anti-inflammatory strategies, emphasizing the importance of pro-resolving lipid mediators in vascular health. This work was supported by funding from Scientific and Technological Research Council of Türkiye (TÜBİTAK) (Project number: 1919B012313469)