Resolvin E1 for reducing vascular calcification.
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ABSTRACT:
SUBMITTER: MacRitchie N
PROVIDER: S-EPMC6648334 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Resolvin E1 for reducing vascular calcification.
MacRitchie Neil N Maffia Pasquale P
Cardiovascular research 20190801 10
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Project description: Not available
| S-EPMC2884679 | biostudies-literature
Project description:The potential of omega-3 poly-unsaturated fatty acids (PUFAs) as a therapeutic target for psoriasis, a chronic inflammatory skin disease of IL-23/IL-17 axis, is a long-disputed question, since various epidemiological studies have suggested the association between high-intake of omega-3 PUFAs and the reduced frequency and severity of psoriasis. However, their actual significance and the molecular mechanisms remain largely unknown. To address these issues, we focused on resolvin E1 (RvE1), an omega-3 PUFAs-derived metabolite, and examined its effects on psoriatic dermatitis, using an imiquimod-induced mouse psoriasis model. RvE1 potently suppressed the inflammatory cell infiltration and epidermal hyperplasia in the psoriatic skin. RvE1 decreased the mRNA expression of IL-23 in the skin. Consistently, RvE1 inhibited IL-23 production by dendritic cells (DCs) in vitro. Furthermore, RvE1 exerted inhibitory effects on migration of cutaneous DCs and γδ T cells, a major IL-17-producing cell population in mouse, both in vivo and in vitro. These suppressive effects of RvE1 were mediated by its antagonistic function on BLT1, a receptor of leukotriene B4, and were also observed in human DCs, Th17 and Tc17 cells. Our results indicate a novel mechanism of omega-3 PUFA-mediated amelioration of psoriasis, and suggest a potential of RvE1 as a therapeutic target for psoriasis.
| S-EPMC6082864 | biostudies-literature
Project description:Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota.
| S-EPMC5026932 | biostudies-literature
Project description:Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown. Aortic ChemR23 expression was increased in Ang II-induced hypertensive mice and that ChemR23 was mainly expressed on vascular smooth muscle cells (VSMCs). RvE1 lowered blood pressure, reduced aortic media thickness, attenuated aortic fibrosis, and mitigated VSMC phenotypic transformation and proliferation in hypertensive mice, which were all reversed by the knockdown of ChemR23. Moreover, RvE1 reduced the aortic infiltration of macrophages and T cells, which was also reversed by ChemR23 knockdown. RvE1 inhibited Ccl5 expression in VSMCs via the AMPKα (AMP-activated protein kinase α)/Nrf2 (nuclear factor E2-related factor 2)/canonical NF-κB (nuclear factor κB) pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKα/Nrf2 pathway also mediated the effects of RvE1 on VSMC phenotypic transformation and proliferation. In patients with hypertension, the serum levels of RvE1 and other eicosapentaenoic acid-derived metabolites were significantly decreased
2025-05-01 | GSE283472 | GEO
Project description:Resolvins are endogenous lipid mediators that actively regulate the resolution of acute inflammation. Resolvin E1 (RvE1; (5S,12R,18R)-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) is an endogenous anti-inflammatory and pro-resolving mediator derived from eicosapentaenoic acid that regulates leukocyte migration and enhances macrophage phagocytosis of apoptotic neutrophils to resolve inflammation. In the inflammatory milieu, RvE1 mediates counter-regulatory actions initiated via specific G protein-coupled receptors. Here, we have identified RvE1-specific signaling pathways initiated by the RvE1 receptor ChemR23. RvE1 stimulated phosphorylation of Akt that was both ligand- and receptor-dependent. RvE1 regulated Akt phosphorylation in a time (0-15 min)- and dose-dependent (0.01-100 nm) manner in human ChemR23-transfected Chinese hamster ovary cells. RvE1 stimulated phosphorylation of both Akt and a 30-kDa protein, a downstream target of Akt, identified using a phospho-Akt substrate antibody. The 30-kDa protein was identified as ribosomal protein S6, a translational regulator, and its phosphorylation was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) and an ERK inhibitor (PD98059) but not by a p38-MAPK inhibitor (SB203580). Ribosomal protein S6 is a downstream target of the PI3K/Akt signaling pathway as well as the Raf/ERK pathway. In ChemR23-expressing differentiated HL60 cells, RvE1 also stimulated the phosphorylation of ribosomal protein S6. In addition, RvE1 enhanced phagocytosis of zymosan A by human macrophages, which are inhibited by PD98059 and rapamycin (mTOR inhibitor). These results indicate that RvE1 initiates direct activation of ChemR23 and signals receptor-dependent phosphorylation. These phosphorylation-signaling pathways identified for RvE1 receptor-ligand interactions underscore the importance of endogenous pro-resolving agonists in resolving acute inflammation.
| S-EPMC2823415 | biostudies-literature
Project description:Resolvin E1 (RvE1) is a specialized pro-resolving lipid mediator derived from eicosapentaenoic acid and plays a critical role in resolving inflammation and tissue homeostasis. Th17 cells are a distinct group of T helper (Th) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases via the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the Th17-induced progression of inflammation and tissue destruction. In this study, we hypothesized that the RvE1 would restore homeostatic balance and inflammation by targeting the Th17 function. We designed three experiments to investigate the impact of RvE1 on different phases of Th17 response and the potential role of DCs: First CD4+ T cells were induced by IL-6/TGFβ to measure the effect of RvE1 on Th17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated Th17 differentiation in a co-culture model. Third, we measured the effect of RvE1 on DC maturation. RvE1 blocked the CD25, CCR6 and IL-17 expression; IL-17, IL-21, IL-10, and IL-2 production, suggesting inhibition of T cell activation, Th17 stimulation and chemoattraction. RvE1 also suppressed the activation of DCs by limiting their pro-inflammatory cytokine production. Our findings collectively demonstrated that the RvE1 targeted the Th17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.
| S-EPMC8009993 | biostudies-literature
Project description:Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases--pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators--caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues.
| S-EPMC2757086 | biostudies-literature
Project description:The polyunsaturated ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvE1 are characterized, the molecular mechanism of its bone-protective actions are of interest. To test the hypothesis that receptor-mediated events impact bone changes, we prepared transgenic mice overexpressing the RvE1 receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvE1 was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvE1 treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvE1 significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-κB ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvE1 modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-κB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions.
| S-EPMC3538964 | biostudies-literature
Project description:Resolvin E1 is a metabolite of eicosapentaenoic acid (EPA) which is one of the omega-3 polyunsaturated fatty acids (omega-3 PUFAs). The antiplatelet properties of omega-3 PUFAs are well known, but the effect of resolvin E1 on platelets via the collagen receptors is extremely poorly reported. We investigated the effect of resolvin E1 on collagen-induced platelet aggregation, activation, and reactivity, and also platelet membrane fluidity. The ultimate and statistically significant results showed that resolvin E1 may inhibit platelet reactivity due to the reduction of collagen-induced platelet aggregation in platelet-rich plasma and isolated platelets, but not in whole blood. Also, resolvin E1 significantly reduced P-selectin exposure on collagen-stimulated platelets. Moreover, we demonstrated that resolvin E1 can maintain platelet membrane structure (without increasing membrane fluidity). The association between platelet reactivity and membrane fluidity, including resolvin E1 and collagen receptors requires further research. However, the goal of this study was to shed light on the molecular mechanisms behind the anti-aggregative effects of resolvin E1 on platelets, which are still not fully clarified. We also indicate an innovative research direction focused on further analysis and then use of omega-3 PUFAs metabolites as antiplatelet compounds for future applications in the treatment and prevention of cardiovascular diseases.
| S-EPMC10385542 | biostudies-literature
Project description:Background and purposeThe ω-6 fatty acid-derived lipid mediators such as prostanoids, thromboxane and leukotrienes have well-established roles in regulating both inflammation and smooth muscle contractility. Resolvins are derived from ω-3 fatty acids and have important roles in promoting the resolution of inflammation, but their activity on smooth muscle contractility is unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic aorta (RTA) or human pulmonary artery (HPA) induced by the α1 -adrenoceptor agonist phenylephrine or the stable thromboxane A2 mimetic U46619.Experimental approachContractile responses in RTA and HPA were measured using wire myography. Receptor expression was investigated by immunohistochemistry.Key resultsConstriction of RTA segments by U46619, but not by phenylephrine, was significantly inhibited by pretreatment for 1 or 24 h with 10-100 nM RvE1, RvD1 or RvD2. The inhibitory effect of RvE1 was partially blocked by a chemerin receptor antagonist (CCX832). RvE1 at only 1-10 nM also significantly inhibited U46619-induced constriction of HPA segments, and the chemerin receptor, GPR32 and FPR2/ALX were identified in HPA smooth muscle.Conclusion and implicationsThese data suggest that resolvins or their mimetics may prove useful novel therapeutics in diseases such as pulmonary arterial hypertension, which are characterized by increased thromboxane contractile activity.
| S-EPMC5843708 | biostudies-literature