The expansive role of oxylipins on platelet biology

Yeung, Jennifer; Hawley, Megan; Holinstat, Michael

doi:10.1007/s00109-017-1542-4

Cited by 80 publications

(91 citation statements)

References 130 publications

(121 reference statements)

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“…Bioactive lipids formed in the platelet following initial activation play a significant role in reinforcing the primary signal initiated through thrombin and collagen [9]. The majority of the lipid products are formed by oxidation of free fatty acids to their oxidized active forms.…”

Section: Platelet Role In Hemostasis and Thrombosismentioning

confidence: 99%

Normal platelet function

Holinstat

2017

Cancer Metastasis Rev

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322

225

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Platelets play an important role in the vessel. Following their formation from megakaryocytes, platelets exist in circulation for 5–7 days and primarily function as regulators of hemostasis and thrombosis. Following vascular insult or injury, platelets become activated in the blood resulting in adhesion to the exposed extracellular matrix underlying the endothelium, formation of a platelet plug, and finally formation and consolidation of a thrombus consisting of both a core and shell. In pathological conditions, platelets are essential for formation of occlusive thrombus formation and as a result are the primary target for prevention of arterial thrombus formation. In addition to regulation of hemostasis in the vessel, platelets have also been shown to play an important role in innate immunity as well as regulation of tumor growth and extravasations in the vessel. These primary functions of the platelet represent its normal function and versatility in circulation.

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Section: Platelet Role In Hemostasis and Thrombosismentioning

confidence: 99%

Normal platelet function

Holinstat

2017

Cancer Metastasis Rev

Self Cite

322

225

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“…(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (60). Thus, inhibiting PLA2 activity or increasing omega-3 PUFA levels, which are metabolized to bioactive lipids with anti-inflammatory activity, could potentially reduce disease severity.…”

Section: Nonetheless Blanco-melo and Colleagues Reported A Blunted Imentioning

confidence: 99%

COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status

Thomas

Stefanoni

et al. 2020

Preprint

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Previous studies suggest a role for systemic reprogramming of host metabolism during viral pathogenesis to fuel rapidly expanding viral proliferation, for example by providing free amino acids and fatty acids as building blocks. In addition, general alterations in metabolism can provide key understanding of pathogenesis. However, little is known about the specific metabolic effects of SARS-COV-2 infection. The present study evaluated the serum metabolism of COVID-19 patients (n=33), identified by a positive nucleic acid test of a nasopharyngeal swab, as compared to COVID-19-negative control patients (n=16). Targeted and untargeted metabolomics analyses specifically identified alterations in the metabolism of tryptophan into the kynurenine pathway, which is wellknown to be involved in regulating inflammation and immunity. Indeed, the observed changes in tryptophan metabolism correlated with serum interleukin-6 (IL-6) levels. Metabolomics analysis also confirmed widespread dysregulation of nitrogen metabolism in infected patients, with decreased circulating levels of most amino acids, except for tryptophan metabolites in the kynurenine pathway, and increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and kidney dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis in COVID-19 patients.Metabolite levels in these pathways correlated with clinical laboratory markers of inflammation and disease severity (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen). In conclusion, this initial observational study of the metabolic consequences of COVID-19 infection in a clinical cohort identified amino acid metabolism (especially kynurenine and cysteine/taurine) and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.

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“…Beyond these early reports on the crucial role of ArA oxygenated metabolism in platelet physiology and pathophysiology, other polyunsaturated fatty acids (PUFA), especially from the omega-3 family, have been considered to affect platelet function. A recent review [9] gives an overall view on possible/putative activities of all the known PUFA oxygenated products on platelet function. However, only few of the oxylipins reported to act on platelets are produced by them.…”

Section: Abstract: Platelet Aggregation Aging Diabetes Peroxidation Ementioning

confidence: 99%

Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

Lagarde

Guichardant

Bernoud-Hubac

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The oxygenation metabolism of arachidonic acid (ArA) has been early described in blood platelets, in particular with its conversion into the potent labile thromboxane A that induces platelet aggregation and vascular smooth muscle cells contraction. In addition, the primary prostaglandins D and E have been mainly reported as inhibitors of platelet function. The platelet 12-lipoxygenase (12-LOX) product, i.e. the hydroperoxide 12-HpETE, appears to stimulate platelet ArA metabolism at the level of its release from membrane phospholipids through phospholipase A (cPLA) and cyclooxygenase (COX-1) activities, the first enzymes in prostanoid production cascade. Also, 12-HpETE may regulate the oxygenation of other polyunsaturated fatty acids (PUFA) by platelets, especially that of eicosapentaenoic acid (EPA). On the other hand, the reduced product of 12-HpETE, 12-HETE, is able to antagonize TxA action. This is even more obvious for the 12-LOX end-products from docosahexaenoic acid (DHA), 11- and 14-HDoHE. In addition, 12-HpETE plays a key role in platelet oxidative stress as observed in pathophysiological conditions, but may be regulated by DHA with a bimodal way according to its concentration. Other oxygenated products of PUFA, especially omega-3 PUFA, produced outside platelets may affect platelet functions as well.

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The expansive role of oxylipins on platelet biology

Cited by 80 publications

References 130 publications

Normal platelet function

Normal platelet function

COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status

Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

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