Aspirin inhibits the production of proangiogenic 15(<i>S</i>)‐HETE by platelet cyclooxygenase‐1

Rauzi, Francesca; Kirkby, Nicholas S.; Edin, Matthew L.; Whiteford, James R.; Zeldin, Darryl C.; Mitchell, Jane A.; Warner, Timothy D.

doi:10.1096/fj.201600530r

Cited by 50 publications

(53 citation statements)

References 26 publications

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“…Platelets can produce significant amounts of TXA 2, PGE 2 , PGD 2 , 11‐, 12‐ and 15‐HETE dependent upon the activity of cytosolic group IV A PLA 2 , a widely expressed PLA 2 isoform (Kirkby et al, ; Rauzi et al, ). Below, we will discuss platelet and non‐platelet‐derived eicosanoids whose actions modulate platelet function and consequentially haemostasis and thrombosis (Figure ).…”

Section: Eicosanoids and The Fine Regulation Of Platelet Function Andmentioning

confidence: 99%

“…12‐HETE is the major 12‐LOX‐catalysed metabolite and the most abundant eicosanoid produced by platelets upon stimulation (Kirkby et al, ; Rauzi et al, ), but its effects on platelet function are not completely understood. Initial studies suggested that both 12‐HETE and 14‐hydroxy‐docosahexaenoic acid (14‐OH‐DHA), the 12‐LOX‐derived metabolite of DHA, inhibit platelet aggregation initiated by the TP receptor agonist U46619 (Croset et al, ).…”

Section: Eicosanoids and The Fine Regulation Of Platelet Function Andmentioning

confidence: 99%

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Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

Crescente

Menke

Chan

et al. 2018

British J Pharmacology

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Platelets are important players in thrombosis and haemostasis with their function being modulated by mediators in the blood and the vascular wall. Among these, eicosanoids can both stimulate and inhibit platelet reactivity. Platelet Cyclooxygenase (COX)-1-generated Thromboxane (TX)A is the primary prostanoid that stimulates platelet aggregation; its action is counter-balanced by prostacyclin, a product of vascular COX. Prostaglandin (PG)D , PGE and 12-hydroxyeicosatraenoic acid (HETE), or 15-HETE, are other prostanoid modulators of platelet activity, but some also play a role in carcinogenesis. Aspirin permanently inhibits platelet COX-1, underlying its anti-thrombotic and anti-cancer action. While the use of aspirin as an anti-cancer drug is increasingly encouraged, its continued use in addition to P Y receptor antagonists for the treatment of cardiovascular diseases is currently debated. Aspirin not only suppresses TXA but also prevents the synthesis of both known and unknown antiplatelet eicosanoid pathways, potentially lessening the efficacy of dual antiplatelet therapies.

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Section: Eicosanoids and The Fine Regulation Of Platelet Function Andmentioning

confidence: 99%

Section: Eicosanoids and The Fine Regulation Of Platelet Function Andmentioning

confidence: 99%

Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

Crescente

Menke

Chan

et al. 2018

British J Pharmacology

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“…also used an assay volume of 150 μl, albeit with different ratios of PRP to agonist (10,16). A few groups have used an assay volume of more than 150 μl (15,17,19), but most have reduced volumes of PRP or washed platelets to around 100 μl (9,11,20–22). As a result, for the same volume of blood collected from a patient, a greater selection of agonists and concentrations may be studied using this assay that using LTA.…”

Section: -Well Plate Aggregationmentioning

confidence: 99%

“…The majority of this work concerns the characterization of platelet reactivity in the presence of antiplatelet therapies such as GPIIb/IIIa inhibitors (16,23) or dual anti-platelet therapy with ADP P2Y 12 antagonists plus aspirin (10–13,17,21,22,25,26). Using these techniques, it is possible to produce concentration-response curves which can be used to evaluate the pharmacological action of these therapies.…”

Section: -Well Plate Aggregationmentioning

confidence: 99%

96-well plate-based aggregometry

2018

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While there are many bench and bedside tests to assess platelet reactivity, ex vivo light transmission aggregometry (LTA) remains the gold standard. LTA, however, is expensive, time-consuming and requires dedicated equipment and staff, making it impractical in many situations. In addition, there is significant variability between data generated at different testing sites meaning that tests often need to be repeated if a patient is transferred to the care of a different hospital. As such, there is clearly an unmet need for standardization of platelet testing.Using the principles of LTA, aggregometry can be conducted in 96-well plates with readings being made in a standard plate reader. This approach allows for the assessment of multiple concentrations of agonists, since the volume of platelets required for each test is significantly lower than for LTA. Furthermore, the lyophilization of a set panel of agonists to a 96-well plate to produce a stable assay substrate allows the production of portable, standardized plates that can be used to generate reproducible tests at multiple sites.In this review, we will discuss the methods and uses of 96-well plate aggregometry for both research and the clinic.

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“…In fact, angiogenesis is a common target of many cancer chemopreventive agents including aspirin and curcumin . Mechanistically, aspirin inhibits the production of 11‐hydroxyeicosatetraeoic acid and 15 (S)‐ hydroxyeicosatetraenoic acid from platelets, which can induce endothelial cell migration and the formation of tubular structure . In addition, the proangiogenic heparanase is a novel target of aspirin .…”

Section: Complex Mechanisms For the Anticancer Effects Of Aspirinmentioning

confidence: 99%

Complex roles of the old drug aspirin in cancer chemoprevention and therapy

Hua

Zhang

Kong

et al. 2018

Medicinal Research Reviews

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The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin.

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Aspirin inhibits the production of proangiogenic 15(S)‐HETE by platelet cyclooxygenase‐1

Cited by 50 publications

References 26 publications

Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

96-well plate-based aggregometry

Complex roles of the old drug aspirin in cancer chemoprevention and therapy

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