TP or Not TP: Primary Mediators in a Close Runoff?

Praticò, Domenico; Cheng, Yan; FitzGerald, Garret A.

doi:10.1161/01.atv.20.7.1695

Cited by 19 publications

(11 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, terutroban inhibits the platelet and vascular action of TXA 2 released from extraplatelet sources, such as monocyte COX-2, as well as that of other eicosanoids [20], which are insensitive to aspirin [21] and whose production is increased in atherosclerosis. In this respect, there is strong evidence that terutroban inhibits the development of atherosclerotic lesions by a mechanism independent of platelet TXA 2 production, most probably as a result of the inhibition of the effect of eicosanoids of extraplatelet origin, such as isoprostanes [20,22].…”

Section: Discussionmentioning

confidence: 99%

“…With regards to bleeding time, there was an increase vs. baseline with both terutroban and aspirin. Changes in bleeding time from baseline to last value on treatment slightly increased in a dose-dependent manner with terutroban (22,61,53, 123 and 123 s in 1, 2.5, 5, 10 and 30 mg, respectively). By comparison, the effect of aspirin was similar to the effect of the highest dosages of terutroban (Table 3).…”

Section: P-valuementioning

confidence: 91%

See 1 more Smart Citation

Thromboxane Antagonism with terutroban in Peripheral Arterial Disease: the TAIPAD study

Fiessinger

Bounameaux

Cairols

et al. 2010

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary. Background: Terutroban is a selective prostaglandin endoperoxide (TP) receptor antagonist with antithrombotic, antivasoconstrictive and antiatherosclerotic properties and is currently in development for long‐term cardiovascular secondary prevention. Objectives: TAIPAD is an international, double‐blind, randomized controlled study comparing the effects of five dosages of oral terutroban vs. aspirin and placebo on platelet aggregation in peripheral arterial disease (PAD) patients. Patients/methods: After 10 day’s placebo run‐in, included patients (n = 435; ankle‐brachial pressure index, 0.7 ± 0.1) were randomly allocated to aspirin 75 mg day−1, terutroban 1, 2.5, 5, 10 or 30 mg day−1 or placebo. On day 5, the placebo group was reallocated to one of the terutroban groups for the rest of the study (day 83). Ex vivo platelet aggregation induced by the thromboxane analog U46619 (7 μm) was measured 24 h after dosing, as well as platelet aggregation induced by arachidonic acid (AA), collagen and ADP. Results: Terutroban dose‐dependently inhibited U46619‐induced platelet aggregation at days 5 and 83. At day 5, the inhibition was significant vs. placebo for all terutroban dosages (P < 0.001). Terutroban (5, 10 and 30 mg day−1) was at least as effective as aspirin in inhibiting platelet aggregation induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Terutroban was well tolerated, with a safety profile similar to aspirin. Conclusions: In PAD patients, terutroban dose‐dependently inhibited platelet aggregation 24 h after dosing, and was at least as effective as aspirin at 5, 10 and 30 mg day−1. Terutroban was well tolerated.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: P-valuementioning

confidence: 91%

Thromboxane Antagonism with terutroban in Peripheral Arterial Disease: the TAIPAD study

Fiessinger

Bounameaux

Cairols

et al. 2010

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Dual inhibitors of both these activities such as CV6504 [130] may serve as a basis in the development of next generation of drugs against atherosclerosis, although they are not currently developed for this indication. In addition to the COX and LO pathway of AA metabolism, generation of non-enzymatic products of arachidonate termed isoprostanes is increased in both humans with atherosclerosis and in ApoE-knockout mice [131].…”

Section: Enzymes Of the Eicosanoid Cascadementioning

confidence: 99%

Macrophage Differentiation to Foam Cells

Shashkin¹,

Dragulev²,

Ley³

2005

CPD

249

159

View full text Add to dashboard Cite

Foam cell formation from macrophages with subsequent fatty streak formation plays a key role in early atherogenesis. Foam cell formation is thought to be induced by Low Density Lipoproteins (LDL), including oxidized LDL (OxLDL) or minimally modified LDL (mmLDL). Understanding the molecular mechanisms involved in OxLDL-and mmLDL-induced foam cell formation is of fundamental importance for atherosclerosis and cardiovascular disease. The expression of many genes is likely modulated during macrophage transformation into a foam cell. In this mini-review we describe functional consequences of modulation of three groups of genes: Scavenger Receptors (SR-A, CLA-1/SR-BI, CD36, CD68, LOX-1, and SR-PSOX), the PPAR family of nuclear receptors, and a number of genes involved in eicosanoid biosynthesis, including lipoxygenases and leukotriene receptors. Scavenger receptors appear to play a key role in uptake of OxLDL, while mmLDL appears to interact with CD14/TLR4. The regulation of scavenger receptors is, in part, mediated by the PPAR family of nuclear receptors. PPARα and PPARγ agonists, such as thiazolidinediones and fibrates, and PPARδ agonists were tested as atheroprotective drugs and showed some beneficial effects. Eicosanoids are naturally occuring agonists for PPARs. Recent observations indicate a role of the components of the eicosanoid cascade, such as 5-lipoxygenase, 15-lipoxygenase and the leukotriene receptors in foam cell formation. Selective inhibitors of lipoxygenases and leukotriene receptors could be useful in the treatment of atherosclerosis by preventing or reducing foam cell formation.

show abstract

“…The other target that needs to be considered to slow the progression of atherosclerosis and its sequelae is the TP receptor. 18,19 TP receptor antagonists may have significant potential therapeutic benefit in preventing not only the progression of atherosclerosis but also the acute cardiovascular events associated with it. Perhaps the ideal future therapeutic approach to treating the acute and chronic sequelae of atherosclerosis is the combination of a TP receptor antagonist and a selective COX-2 inhibitor.…”

Section: See P 1650mentioning

confidence: 99%