Anti-Phospholipid Antibodies and Impairment of Prostacyclin Synthesis by the Endothelium

2020 ◽  
pp. 231-245 ◽  
Author(s):  
Luis O. Carreras ◽  
Jos Vermylen
Keyword(s):  
Prostacyclin Synthesis

Prostacyclin Synthesis Is Stimulated by a Serum Factor Formed During Coagulation

1983 ◽  
Vol 49 (01) ◽  
pp. 058-060 ◽  
Author(s):  
J M Ritter ◽  
M-A Ongari ◽  
M A Orchard ◽  
P J Lewis
Keyword(s):  
Renal Failure ◽  
Hydrolysis Product ◽  
Healthy Controls ◽  
Serum Factor ◽  
Intrinsic Pathway ◽  
Extrinsic Pathway ◽  
Stimulatory Activity ◽  
Plasma Factor ◽  
Stimulating Factor ◽  
Prostacyclin Synthesis

SummaryFresh aortic rings incubated in serum produce more 6-oxo-PGF1α, the stable hydrolysis product of prostacyclin, than in plasma or buffer. A method is described of recovering this stimulatory activity from a dialysate of serum, showing that the activity is due to a prostacyclin stimulating factor. This factor is formed during coagulation initiated by the intrinsic pathway but not by the extrinsic pathway or by thrombin. By contrast with a previously described plasma factor, the activity of the prostacy-clinstimulating factor in serum is not greater in serum from patients with renal failure than from healthy controls. The stimulating factor is antagonised by heparin, but differs in other ways from previously described platelet derived stimulating factor(s).

Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits

1979 ◽  
Author(s):  
J McDonald ◽  
A Cerskus ◽  
M Ali
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Low Dose ◽  
High Dose ◽  
Prostacyclin Synthesis

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PGF1α. The effects of pretreatement with aspirin (ASA) or sulfinpyrazone(SPZ) were assessed.Death in drug-treated rabbits was always associated with elevations of plasma TXB2(1-40 ng/ml) and of 6-keto-PGF1α(1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.

Engineering ‘Enzymelink’ for screening lead compounds to inhibit mPGES-1 while maintaining prostacyclin synthase activity

2021 ◽  
Author(s):  
Diana T Ruan ◽  
Nanhong Tang ◽  
Hironori Akasaka ◽  
Renzhong Lu ◽  
Ke-He Ruan
Keyword(s):  
Significant Degree ◽  
Hek293 Cells ◽  
Synthesis Methods ◽  
Compound Library ◽  
Lead Compounds ◽  
Cox 2 ◽  
Targeted Drug Discovery ◽  
Prostacyclin Synthase ◽  
Large Compound ◽  
Prostacyclin Synthesis

Aim: This study investigated our Enzymelinks, COX-2-10aa-mPGES-1 and COX-2-10aa-PGIS, as cellular cross-screening targets for quick identification of lead compounds to inhibit inflammatory PGE2 biosynthesis while maintaining prostacyclin synthesis. Methods: We integrated virtual and wet cross-screening using Enzymelinks to rapidly identify lead compounds from a large compound library. Results: From 380,000 compounds virtually cross-screened with the Enzymelinks, 1576 compounds were identified and used for wet cross-screening using HEK293 cells that overexpressed individual Enzymelinks as targets. The top 15 lead compounds that inhibited mPGES-1 activity were identified. The top compound that specifically inhibited inflammatory PGE2 biosynthesis alone without affecting COX-2 coupled to PGI2 synthase (PGIS) for PGI2 biosynthesis was obtained. Conclusion: Enzymelink technology could advance cyclooxygenase pathway-targeted drug discovery to a significant degree.

Sign in / Sign up

Export Citation Format

Share Document