Prostacyclin synthesis

Omega-3 fatty acids and increased prostacyclin synthesis. 

Besides cholesterol efflux from arterial wall and its role in RCT, additional properties of HDL have been proposed for its protective anti-atherogenic activities. HDL protects vascular function by a number of potential alternative mechanisms, including inhibition of LDL oxidation [8,9], platelet aggregation and coagulation [10], and endothelial monocyte adhesion [11], as well as promotion of endothelial nitric oxide synthase (eNOS) [12], and prostacyclin synthesis [13-15]. The proposed alternate protective mechanisms for HDL are attractive but many of them lack validation under in vivo conditions. 

Ageel, M. A. A. Nasif, and E. A. Gadkarim. Effects of sesame and cod SI 137 liver oils on prostacyclin synthesis by the rat thoracic aorta. Arch Int Pharmacodyn Ther 1988 292(1) ... 

Ea-Kim, L., Javellaud, J., Oudart, N., 1992b. Endothelium-dependent relaxation of rabbit middle cerebral artery to a histamine H3-agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis. Br. J. Pharmcol. 105, 103-106. 

Dazoxiben, an inhibitor of thromboxane-Aj but not of prostacyclin synthesis, is being evaluated in cardiovascular disease. 

Hanley SP, Bevan J, Cockbill SR, Heptinstall S. Differential inhibition by low-dose aspirin of human venous prostacyclin synthesis and platelet thromboxane synthesis. Lancet 1981 1(8227) 969-71. 

Neagoe, PE, Eemieux, C Sirois, MG. Vascular endothelial growth factor (VEGF)-A165-induced prostacyclin synthesis requires the activation of VEGE receptor-1 and -2 heterodimer. J Biol Chem, 280 9904-12, 2005. 

Nakamura, H., Kim, D.K., Philbin, D.M., Peterson, M.B., Debros, F., Koski, G., and Bonventre, J.V. Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients un-... 

Prostacyclins and thromboxanes, synthesis of 84S449 79T2705. Prostaglandin endoperoxides, thromboxanes, prostacyclins, synthesis and... 

Dietary intake of n-6 fatty acids such as linoleic acid, and n-3 fatty acids, such as the fish oils eicosapentanoic acid and docosahexaenoic acid, lowers plasma cholesterol and antagonizes platelet activation, but the fish oils are much more potent in this regard [26]. In particular, n-3 fatty acids competitively inhibit thromboxane synthesis in platelets but not prostacyclin synthesis in endothelial cells. These fatty acids have also been shown to have other potentially anti-atherogenic effects, such as inhibition of monocyte cytokine synthesis, smooth muscle cell proliferation, and monocyte adhesion to endothelial cells. While dietary intake of n-3 fatty acid-rich fish oils appears to be atheroprotective, human and animal dietary studies with the n-6 fatty acid linoleic acid have yielded conflicting results in terms of effects on both plasma lipoproteins and atherosclerosis. Indeed, excess amounts of both n-3 and n-6 fatty acids may actually promote oxidation, inflammation, and possibly atherogenesis (M. Toberek, 1998). In this context, enzymatic and non-enzymatic oxidation of linoleic acid in the sn-2 position of LDL phospholipids to 9- and 13-hydroxy derivatives is a key event in LDL oxidation (Section 6.2). 

PGE2 and PGF2CI stimulate synthesis of protective mucus in stomach and in small intestine. When ASA is administrated, prostaglandins and prostacyclins synthesis is blocked and acid secretion is increased, reducing mucosae protection. COX has two different isoforms COX-1, expressed in most tissues and implicated in the regulation of normal homeostatic functions such as gastric acid secretion and COX-2, induced often by inflammatory processes. As a result, COX-2 is implicated in the production of pro-inflammatory eicosanoids (see Figure 25). In feet, one of the therapeutic actions of ASA et similia NSAIDs has been the inhibition of COX activity to reduce pro-inflammatory eicosanoids [73]. 

Prostacyclins (PGI2) mediate vasodilatation and also stimulate the secretion of renin. Thus, they increase renal blood flow. Inhibition of prostacyclin synthesis by high doses of NSAIDs, therefore, can be detrimental to kidney function. 

The thioallyl anion from (132) reacts with cyclopentadiene oxide (133) in THF at -78°C to give (134 R1=2-PyrS,R2,R =bond) (62 ) which was transformed into the allyl alcohol (134 R R bond, R =0H) (713S) as part of a prostacyclin synthesis. ... 

---