E-series resolvin biosynthesis pathway (RvE pathway)

The E-series resolvin biosynthesis pathway is a critical biochemical sequence responsible for producing specialized pro-resolving mediators (SPMs) from the omega-3 fatty acid eicosapentaenoic acid (EPA) (Serhan, C. N., Nature, 2014). This pathway is initiated by either cytochrome P450 enzymes or aspirin-acetylated cyclooxygenase-2 (COX-2), which convert EPA into 18R-hydroxyeicosapentaenoic acid (18R-HEPE) (Arita, M., et al., J Exp Med, 2005). Subsequent processing by 5-lipoxygenase (5-LOX) leads to the formation of Resolvin E1 (RvE1) and Resolvin E2 (RvE2), while 12/15-lipoxygenase is involved in the production of Resolvin E3 (RvE3) (Isobe, Y., et al., J Biol Chem, 2012). These E-series resolvins play a pivotal role in the active resolution phase of inflammation by binding to specific G protein-coupled receptors, such as ChemR23 (ERV1) and BLT1, to inhibit neutrophil infiltration and promote the clearance of apoptotic cells by macrophages (Serhan, C. N., & Petasis, N. A., Chem Rev, 2011). Dysregulation of this pathway is linked to chronic inflammatory conditions, including cardiovascular disease, rheumatoid arthritis, and asthma (Dalli, J., et al., Nature Medicine, 2013). Therapeutic strategies targeting this pathway include the administration of EPA, aspirin to trigger 'aspirin-triggered' resolvins, or synthetic resolvin analogs like RX-10045 designed to treat inflammatory disorders (Spite, M., et al., Circ Res, 2014). These interventions aim to promote the natural resolution of inflammation without the immunosuppressive side effects often associated with traditional anti-inflammatory drugs.

Other names

Resolvin E biosynthesisEPA-derived specialized pro-resolving mediator pathwayRvE biosynthesis pathwayE-series SPM pathway

The pathway facilitates the enzymatic conversion of eicosapentaenoic acid (EPA) into bioactive E-series resolvins (RvE1, RvE2, RvE3) via cytochrome P450 or aspirin-acetylated COX-2 and lipoxygenases; these mediators then activate specific G protein-coupled receptors (ChemR23 and BLT1) to signal the termination of the inflammatory response.