Further studies on the anti-thromboxane A2 activity of monohydroxylated fatty acids

Lagarde, Michel; Boutillon, Marguerite‐Marie; Guichardant, Michel; Lellouche, Jean‐Paul; Beaucourt, J. P.; Vanhove, A.; Grée, René

doi:10.1016/0006-2952(89)90422-x

Cited by 19 publications

(9 citation statements)

References 13 publications

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“…Early work from our group showed that monohydroxy derivatives from linoleic acid, AA, EPA, and DHA may antagonize the thromboxane mimetic U-46619 on platelet aggregation, with significantly more potent activity of the 12-lipoxygenase product of DHA (35,36,44). The present work extends the observation to a family of double lipoxygenation end products with a specific E,Z,E-conjugated triene, collectively named poxytrins, which are all active at 8.9 Ϯ 0.4 9.5 Ϯ 0.9 9.6 Ϯ 0.7 54.5 Ϯ 4.5* 71.5 Ϯ 12.8* Platelets were incubated at 37°C in the presence or absence of PDX for 5 min.…”

Section: Discussionmentioning

confidence: 99%

Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

et al. 2010

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Docosahexaenoic acid (DHA), an important component of marine lipids, exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as neuroprotectin/protectin D1 [NPD1/PD1; 10(R),17(S)-dihydroxy-docosa-4Z,7Z, 11E,13E,15Z,19Z-hexaenoic acid] produced through the 15-lipoxygenase pathway. However, other metabolites from DHA can be produced through this pathway, and other polyunsaturated fatty acids (PUFAs) of nutritional value may be oxygenated as well. Their biological activities remain unknown. Isomers of protectin D1 were synthesized using soybean lipoxygenase and tested for their ability to inhibit human blood platelet aggregation. A geometric isomer called PDX, previously described with the 11E,13Z,15E geometry, instead of 11E,13E,15Z in PD1, inhibited platelet aggregation at submicromolar concentrations when induced by either collagen, arachidonic acid, or thromboxane. The inhibition occurred at the level of both the cyclooxygenase activity and thromboxane receptor site. Interestingly, all the metabolites tested exhibiting the E,Z,E-conjugated triene were active, whereas E,E,Z trienes (as in PD1) or all-trans (E,E,E) trienes were inactive. We conclude that PDX and other oxygenated products from PUFAs of nutritional interest, having the E,Z,E-conjugated triene motif and collectively named poxytrins (PUFA oxygenated trienes), might have antithrombotic potential.

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Section: Discussionmentioning

confidence: 99%

Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

et al. 2010

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“…A previous study indicated that 13(R)-HODE exerts an antagonizing effect on thromboxane A 2 -induced platelet aggregation, and that this effect was stronger than that of 13(S)-HODE [12]. This may conflict with another fact that PPARγ agonists including 13-HODE upregulate plasminogen activator inhibitor type-1 (PAI-1) in cultured human endothelial cells [14].…”

Section: Discussionmentioning

confidence: 99%

“…13-Hydroxyoctadecadienoic acid (13-HODE) is one of the major oxidized fatty acids [11, 23] and a major component of OxLDL detected in atherosclerotic lesions [6, 21]. Several studies have demonstrated that 13-HODE exerts anti-inflammatory effects as a ligand of peroxisome proliferator-activated receptor-gamma (PPARγ) [17], promotes macrophage OxLDL uptake [24], and inhibits endothelial cell/platelet interaction [4, 12], cancer cell metastasis and proliferation [18, 20] and triacylglycerol-rich lipoprotein secretion [16]. …”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Detection of 13(R)-hydroxyoctadecadienoic Acid in Atherosclerotic Plaques of Human Carotid Arteries Using a Novel Specific Antibody

Shibata

Toi

Shibata

et al. 2009

Acta Histochem. Cytochem.

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13-Hydroxyoctadecadienoic acid (13-HODE) is a major component of oxidized low density lipoprotein (OxLDL), which has been shown to have a crucial role in atherogenesis. Of the 13-HODE stereoisomers, 13(S)-HODE and 13(R)-HODE, little is known about the latter in contrast to the former. To detect 13(R)-HODE in atherosclerotic lesions, we prepared a mouse monoclonal antibody against 13(R)-HODE. Competitive enzyme-linked immunosorbent assay clarified the selective reaction of a clone mAb 13H1 with both free and bovine serum albumin-conjugated forms of 13(R)-HODE but not other oxidized lipids including 13(S)-HODE. Immunohistochemical analysis revealed the colocalization of 13(R)-HODE immunoreactivity with the OxLDL marker oxidized phophatidylcholine immunoreactivity in vascular endothelial cells, macrophages and migrating vascular smooth muscle cells in atherosclerotic plaques of human carotid arteries. The present results provide in vivo evidence for the formation of 13(R)-HODE in atherosclerotic lesions of carotid arteries.

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“…Interestingly, only the two E,Z,E isomers are active to inhibit blood platelet aggregation and purified cyclooxygenase-1 and -2, with the 9R stereoisomer being the most potent [30], and later called linotrins [16]. The relative higher biological activity of R stereoisomers compared to S ones recalls that such an observation had already been done for the inhibition of platelet aggregation by the 17R isomer of PDX [3], and several R mono-hydroxylated derivatives, compared to their S stereoisomers [31]. This is in agreement with the finding that the 17R isomer of PD1, produced by aspirin treated cells in which COX-2 still makes 17(R)-OOH-22:6, further converted into 10(R),17(R)-diOH-4Z,7Z,11E,13E,15Z-22:6 and called AT-PD1 for aspirin-treated [32], is at least as potent as PD1 [33].…”

Section: Double Lipoxygenation Of Docosahexaenoic and Alpha-linolenicmentioning

confidence: 95%

Biological relevance of double lipoxygenase products of polyunsaturated fatty acids, especially within blood vessels and brain

2019

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The double lipoxygenation of polyunsaturated fatty acids (PUFA) is possible with PUFA having at least three methylene-interrupted double bonds. Several PUFA of the omega-3/n-3 and -6 families may be converted through this route, and the products show interesting inhibitory effects on blood platelet function and cyclooxygenase activities. This review focuses on two main omega-3 PUFA of nutritional interest, namely docosahexaenoic acid (DHA/22:6n-3) and alpha linolenic acid (ALA/18:3n-3). The chemical configuration of the double lipoxygenase end-product from DHA (protectin DX) is compared with that of protectin D1 which is produced through a mono-lipoxygenation step followed by an epoxidation and epoxide hydrolysis process. The different metabolic pathways are discussed as well as the different biological activities of both protectins.

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Further studies on the anti-thromboxane A2 activity of monohydroxylated fatty acids

Cited by 19 publications

References 13 publications

Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation

Immunohistochemical Detection of 13(R)-hydroxyoctadecadienoic Acid in Atherosclerotic Plaques of Human Carotid Arteries Using a Novel Specific Antibody

Biological relevance of double lipoxygenase products of polyunsaturated fatty acids, especially within blood vessels and brain

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