The cyclooxygenase pathway produces thromboxane, prostacyclin and prostaglandin D, E and F . Alternatively, the lipoxygenase enzyme pathway is active in leukocytes and in macrophages and synthesizes leukotrienes.
32.
To overcome this challenge, the research team that discovered prostacyclin was determined to continue the research in an attempt to build upon the success they had seen with the prototype molecule.
33.
Prostacyclin PGI2, an arachadonic acid derived lipid mediator ( Epoprostenol, Flolan, Treprostenil ) is a vasodilator and, at the same time, the most potent inhibitor of platelet aggregation.
34.
Studies with human pharmacology and genetics, genetically manipulated rodents, and other animal models and randomized trials indicate that this is due to suppression of PTGS2 ( COX-2 )-dependent cardioprotective prostaglandins, prostacyclin in particular.
35.
Of special importance are the cytochrome P450 enzymes in animals, including CYP5A1 ( thromboxane synthase ), CYP8A1 ( prostacyclin synthase ), and the CYP74 family of hydroperoxide-metabolizing enzymes in plants, lower animals and bacteria.
36.
As of 2012 results have been converging on the hypothesis that the adverse cardiovascular effects are most likely due to inhibition of COX-2 in blood vessels, which leads to a decrease in the production of prostacyclin in them.
37.
The central and primary event in this progression is injury to the endothelial cells, which reduces the production of prostaglandin and prostacyclin, ultimately resulting in the loss of physiological thromboresistance, or high thrombus formation rate in blood vessels.
38.
Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, by selectively inhibiting PTGS2, prostaglandin production ( specifically, PGI2; prostacyclin ) is downregulated with respect to thromboxane levels, as PTGS1 in platelets is unaffected.
39.
It's just as much an improvement as we saw with our prostacyclin studies in the'80s and'90s, " said the American Heart Association's Dr . Robyn Barst, a director of the New York Presbyterian Pulmonary Hypertension Center.
40.
Allene oxide synthase ( CYP74A; ), fatty acid hydroperoxide lyase ( CYP74B ), prostacyclin synthase ( CYP8; ) and thromboxane synthase ( CYP5; ) are examples of P450 enzymes that do not require a reductase or molecular oxygen for their catalytic activity.
