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

FASEB J

Université de Lyon, Unité Mixte de Recherche (UMR) 870, Institut National de la Santé et de la Recherche Médicale (INSERM)/Institut National des Sciences Appliquées–Lyon, and UMR 1235, Institut National de Recherche Agronomique, Villeurbanne, France.

Published: January 2011

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.

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.10-161836DOI Listing

Publication Analysis

Top Keywords

platelet aggregation
12
oxygenated products
8
polyunsaturated fatty
8
fatty acids
8
blood platelet
8
pufas nutritional
8
eze-conjugated triene
8
oxygenated
5
poxytrins class
4
class oxygenated
4

Similar Publications

Interaction and cleavage of cell and plasma proteins by the platelet-aggregating serine protease PA-BJ of Bothrops jararaca venom.

Biochimie

January 2025

Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil. Electronic address:

PA-BJ is a serine protease present in Bothrops jararaca venom that triggers platelet aggregation and granule secretion by activating the protease-activated receptors PAR-1 and PAR-4, without clotting fibrinogen. These receptors also have a relevant role in endothelial cells, however, the interaction of PA-BJ with other membrane-bound or soluble targets is not known. Here we explored the activity of PA-BJ on endothelial cell receptor, cytoskeleton, and coagulation proteins in vitro, and show the degradation of fibrinogen and protein C, and the limited proteolysis of actin, EPCR, PAR-1, and thrombomodulin.

View Article and Find Full Text PDF

The effect of sarpogrelate compared to aspirin in high- or very-high-risk diabetes for primary prevention.

Sci Rep

January 2025

Gachon Medical Research Institute, Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon, 21565, Republic of Korea.

The benefit of aspirin in primary prevention for atherosclerotic cardiovascular diseases (ASCVD) is questionable due to bleeding complications. We analyzed the Korean National Health Insurance data to compare the efficacy and overall bleeding of sarpogrelate, an antiplatelet agent with lower bleeding risk, versus aspirin in high-/very-high-risk diabetic populations without prior ASCVD. The primary endpoint was net adverse clinical events (NACE), defined as a composite of efficacy and overall bleeding.

View Article and Find Full Text PDF

Background And Aims: Due to the multitude of risk factors outlined in the guidelines, personalised dual antiplatelet therapy (DAPT) guidance after percutaneous coronary intervention (PCI) is complex. A simplified method was created to facilitate the use of risk stratification. We aimed to compare the predictive and prognostic value of the 'Zuidoost Nederland Hart Registratie' (ZON-HR) classification for bleeding risk with the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent DAPT (PRECISE-DAPT) score and to determine the effect of ticagrelor monotherapy versus DAPT in patients with or without high bleeding risk (HBR).

View Article and Find Full Text PDF

Analysis of the effect of platelet function and different doses of ticagrelor after flow diverter treatment of intracranial aneurysms.

Neurosurg Rev

January 2025

Neurosurgery Center, Department of Cerebrovascular Surgery, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Ticagrelor has become the standard drug for the treatment of intracranial aneurysms (IAs) with flow diverters (FDs), but the dosage has not been standardized. The effect of platelet function on clinical and imaging prognosis remains unclear. This study aimed to show the effects of different doses of ticagrelor and platelet aggregation function on the clinical and imaging prognosis after FDs treatment of aneurysms.

View Article and Find Full Text PDF

Background: Acetylsalicylic acid (ASA) has been used in reconstructive microsurgery since the inception of the field. However, when compared to placebo groups, its efficacy is not confirmed. In our study, we hypothesize that the utility of ASA postoperatively in microvascular surgery is not associated with improved outcomes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!