Profiling oxylipins released from human platelets activated through the GPVI collagen receptor

Turnbull, Robert E.; Sander, Katrin N.; Turnbull, James; Goodall, Alison H.

doi:10.1016/j.prostaglandins.2021.106607

Cited by 6 publications

(2 citation statements)

References 66 publications

(115 reference statements)

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“…It is also possible that the 15‐oxylipins might be formed through a 15‐LOX‐independent pathway (Figure 7 ). Indeed, previous studies have suggested that 15‐oxylipins are produced in a COX‐dependent manner in platelets 9 , 58 , 66 and demonstrated that recombinant COX has the ability to metabolize AA into 15(S)‐HETE in vitro. 67 Hence, in future studies, mass spectrometry analysis using pharmacological inhibition of 15‐LOX or COX‐1 in platelets could help to determine which oxygenase might be involved in the formation of the 15‐oxylipins.…”

Section: Discussionmentioning

confidence: 99%

Fatty acids negatively regulate platelet function through formation of noncanonical 15‐lipoxygenase‐derived eicosanoids

Yamaguchi

Hoorebeke

Tourdot

et al. 2023

Pharmacology Res & Perspec

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The antiplatelet effect of polyunsaturated fatty acids is primarily attributed to its metabolism to bioactive metabolites by oxygenases, such as lipoxygenases (LOX). Platelets have demonstrated the ability to generate 15‐LOX‐derived metabolites (15‐oxylipins); however, whether 15‐LOX is in the platelet or is required for the formation of 15‐oxylipins remains unclear. This study seeks to elucidate whether 15‐LOX is required for the formation of 15‐oxylipins in the platelet and determine their mechanistic effects on platelet reactivity. In this study, 15‐HETrE, 15‐HETE, and 15‐HEPE attenuated collagen‐induced platelet aggregation, and 15‐HETrE inhibited platelet aggregation induced by different agonists. The observed anti‐aggregatory effect was due to the inhibition of intracellular signaling including αIIbβ3 and protein kinase C activities, calcium mobilization, and granule secretion. While 15‐HETrE inhibited platelets partially through activation of peroxisome proliferator‐activated receptor β (PPARβ), 15‐HETE also inhibited platelets partially through activation of PPARα. 15‐HETrE, 15‐HETE, or 15‐HEPE inhibited 12‐LOX in vitro, with arachidonic acid as the substrate. Additionally, a 15‐oxylipin‐dependent attenuation of 12‐HETE level was observed in platelets following ex vivo treatment with 15‐HETrE, 15‐HETE, or 15‐HEPE. Platelets treated with DGLA formed 15‐HETrE and collagen‐induced platelet aggregation was attenuated only in the presence of ML355 or aspirin, but not in the presence of 15‐LOX‐1 or 15‐LOX‐2 inhibitors. Expression of 15‐LOX‐1, but not 15‐LOX‐2, was decreased in leukocyte‐depleted platelets compared to non‐depleted platelets. Taken together, these findings suggest that 15‐oxylipins regulate platelet reactivity; however, platelet expression of 15‐LOX‐1 is low, suggesting that 15‐oxylipins may be formed in the platelet through a 15‐LOX‐independent pathway.

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Section: Discussionmentioning

confidence: 99%

Fatty acids negatively regulate platelet function through formation of noncanonical 15‐lipoxygenase‐derived eicosanoids

Yamaguchi

Hoorebeke

Tourdot

et al. 2023

Pharmacology Res & Perspec

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“…It has been well-described that specific inhibition of, e.g., COX-1 also impacts the formation of other enzymatic products, such as 11-HETE and 15-HETE, pointing to complex regulatory mechanisms [ 41 ]. Actually, we did not observe any direct strong effect of γ-IRR, and the apparent differences in eicosanoid concentrations during the analyzed time course may likely have resulted from some background platelet enzymatic activity during storage.…”

Section: Discussionmentioning

confidence: 99%

INTERCEPT Pathogen Reduction in Platelet Concentrates, in Contrast to Gamma Irradiation, Induces the Formation of trans-Arachidonic Acids and Affects Eicosanoid Release during Storage

et al. 2022

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Pathogen inactivation techniques for blood products have been implemented to optimize clinically safe blood components supply. The INTERCEPT system uses amotosalen together with ultraviolet light wavelength A (UVA) irradiation. Irradiation-induced inactivation of nucleic acids may actually be accompanied by modifications of chemically reactive polyunsaturated fatty acids known to be important mediators of platelet functions. Thus, here, we investigated eicosanoids and the related fatty acids released upon treatment and during storage of platelet concentrates for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation, and clot firmness hardly differed between the two treatment groups. In contrast to gamma irradiation, here, we demonstrated that INTERCEPT treatment immediately caused new formation of trans-arachidonic acid isoforms, while 11-hydroxyeicosatetraenoic acid (11-HETE) and 15-HETE were increased and two hydroperoxyoctadecadienoic acid (HpODE) isoforms decreased. During further storage, these alterations remained stable, while the release of 12-lipoxygenase (12-LOX) products such as 12-HETE and 12-hydroxyeicosapentaenoic acid (12-HEPE) was further attenuated. In vitro synthesis of trans-arachidonic acid isoforms suggested that thiol radicals formed by UVA treatment may be responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is reasonable to assume that UVA-induced molecules may have specific biological effects which need to be further investigated.

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Bioactive lipid regulation of platelet function, hemostasis, and thrombosis

Stanger

Holinstat

2023

Pharmacology & Therapeutics

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Profiling oxylipins released from human platelets activated through the GPVI collagen receptor

Cited by 6 publications

References 66 publications

Fatty acids negatively regulate platelet function through formation of noncanonical 15‐lipoxygenase‐derived eicosanoids

Fatty acids negatively regulate platelet function through formation of noncanonical 15‐lipoxygenase‐derived eicosanoids

INTERCEPT Pathogen Reduction in Platelet Concentrates, in Contrast to Gamma Irradiation, Induces the Formation of trans-Arachidonic Acids and Affects Eicosanoid Release during Storage

Bioactive lipid regulation of platelet function, hemostasis, and thrombosis

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