Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase

McMahon, Greg; Jones, Chris I.; Hayes, Paul D.; Naylor, A.R.; Goodall, Alison H.

doi:10.1160/th12-11-0793

Cited by 14 publications

(7 citation statements)

References 39 publications

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“…Similarly, an increased ArA cascade has been reported in platelets incubated with LDL isolated from patients having a metabolic syndrome [71]. In addition, recent studies in humans have shown that the 12-LOX pathway generating 12-HETE, but not thromboxane generation, was associated with heparin-induced platelet activation during carotid endarterectomy [72]. This reinforces the notion that the 12-HETE significance might have been previously neglected [73].…”

Section: Production and Action Of Oxygenated Pufa Derivatives In Oxidsupporting

confidence: 71%

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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Section: Production and Action Of Oxygenated Pufa Derivatives In Oxidsupporting

confidence: 71%

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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“…Heparin binds to LDL-C, VLDL, and Lp(a), and together with fibrinogen forms insoluble precipitates which are then removed by a polycarbonate membrane. Transient platelet activation accompanied by increased formation of 12-HETE due to heparin treatment has been shown previously [31]. In contrast, cascade filtration or membrane differential filtration (MDF) employs a membrane that effectively retains particles bigger than 1000 kD through which the plasma is circulated after separation of the cellular parts of the blood.…”

Section: Discussionmentioning

confidence: 96%

Activation of Lipid Mediator Formation Due to Lipoprotein Apheresis

Weylandt

Schmöcker

Ostermann³

et al. 2019

Nutrients

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Lipoprotein apheresis reliably reduces low-density lipoprotein (LDL) cholesterol in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). Besides lowering lipoproteins and triglycerides, apheresis also decreases levels of essential omega-6 and omega-3 polyunsaturated fatty acids (n-6 and n-3 PUFAs) in blood plasma. In contrast, heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) lipid apheresis might increase the formation of potentially pro-inflammatory and pro-thrombotic lipid mediators derived from n-6 and n-3 PUFAs. The study presented here analyzed lipid mediator profiles in the plasma of patients with hyperlipidemia treated by one of three different apheresis methods, either HELP, direct absorption (DA), or membrane filtration (MDF), in a direct pre- and post-apheresis comparison. Using gas chromatography and liquid chromatography tandem mass spectrometry (LC-MS/MS) we were able to analyze fatty acid composition and the formation of lipid mediators called oxylipins. Our data illustrate—particularly in HELP-treated patients—significant decreases of essential omega-6 and omega-3 polyunsaturated fatty acids in blood plasma but significant increases of PUFA-derived lipoxygenase-, as well as cyclooxygenase- and cytochrome P450-derived lipid mediators. Given that n-3 PUFAs in particular are presumed to be cardioprotective and n-3 PUFA-derived lipid mediators might limit inflammatory reactions, these data indicate that n-3 PUFA supplementation in the context of lipid apheresis treatment might have additional benefits through apheresis-triggered protective n-3 PUFA-derived lipid mediators.

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“…Thus, BPC 157 by naB2 regulation could represent a mechanism to guarantee a suited transient EGR-1 activity following injury [ 39 ]. Supporting may also be the BPC 157-induced decrease of the inflammatory mediators, leukotriene B4 (LTB4), thromboxane B2 (TXB2), and myeloperoxidase (MPO), in both serum and inflamed tissue [ 40 ], largely implicated in heparin-induced platelet activation, the adhesion of leukocytes to the endothelium and concomitant increase in vascular permeability [ 41 ], prolongation of the bleeding time [ 42 ] while low-molecular-weight heparin enoxaparin causes systemic MPO activation [ 43 ]. Lastly, implicated in coagulation disorders as well as in anaphylaxis [ 44 ], in response to stimuli such inflammation and trauma, mast cells degranulate and consequently release heparin [ 45 ] while BPC 157 pretreatment significantly prevented mastocyte infiltration [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

et al. 2015

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BackgroundBPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin.MethodsTail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination.ResultsAfter (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia.ConclusionsL-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

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Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase

Cited by 14 publications

References 39 publications

Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

Oxygenation of polyunsaturated fatty acids and oxidative stress within blood platelets

Activation of Lipid Mediator Formation Due to Lipoprotein Apheresis

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

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