Prostacyclins roles

Studies also suggested that IL-6 causes endothelial cell dysfunction and decrease of prostacyclin production. Soluble IL-6 receptors seem to play a modulating and enhancing role in IL-6 activity (FI 8). The incidence of detection appears to be less influenced by the method of assay, as either ELISA or bioassay techniques yield consistent results, with a high correlation between these techniques. IL-6 values may be more constant and endocrine-like than those values of TNF and IL-1. 

Lipids have multiple roles in cells. Recent discoveries show that the same lipid may have both structural and regulatory roles in the cell. For example, while arachidonic acid (20 4co6) is a major constituent of brain inositides and PtdEtn, the free acid is also a precursor of a number of important bio messengers, the eicosanoids, such as prostaglandins, prostacyclins, leukotrienes and thromboxanes... 

Oviedo P, Hermenegildo C, Tartn JJ, Cano A (2005) Raloxifene promotes prostacyclin release in human endothelial cells role of COX-1 and COX-2. Fertil Steril 83 1822-1829... 

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. 

E. Spisni, C. Griffoni, S. Santi, M. Riccio, R. Maulli, G. Bartolini, M. Toni, V. Ullrich, and V. Tomasi. Colocalization prostacycline (PGI2) synthase - caveolin-1 in endothelial cells and new roles for PGI2 in angiogenesis. Exp. Cell Res. 266 31—43 (2001). 

Figure 11.31 Effects of endothelial cells, via prostacyclins, and platelets, via thromboxanes, on aggregation of platelets. Aggregation of platelets plays an important role in thrombosis. The drug inhibited COX-2 and hence prostacyclin formation. However, both COX-1 and COX-2 are present in platelets so COX-1 continues to produce thromboxane.

Prostacyclin (PGIj, 622) appears to play an important role in preventing stroke, thrombosis, and heart attack 361362) this substance is very unstable... 

T. Kobayashi, Y. Tahara, M. Matsumoto, M. Iguchi, H. Sano, T. Murayama, H. Aral, H. Oida, T. Yurugi-Kobayashi, J.K. Yamashita, H. Katagiri, M. Majima, M. Yokode, T. Kita, S. Narumiya, Roles of thromboxane A(2) and prostacyclin in the development of atherosclerosis in apoE-deficient mice, J. Clin. Invest. 114 (2004) 784. 

Arruzazabala, M. L., V. Molina, D. Carbajal, S. Valdes, and R. Mas. Effect of policosanol on cerebral ischemia in Mongolian gerbils role of prostacyclin and thromboxane A2. Prostaglandins Leuko Essent Fatty Acids 1993 49(3) 695-697. 

Luckhoff, A., Pohl, U., Mulsch, A., and Busse, R. (1988). Differential role of extra- and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells. Br. J. Pharmacol. 95, 189-196. 

Phospholipase A2 has an important role in the production of arachidonic acid. This is the precursor of some very important signal molecules such as the prostaglandins, prostacyclins, thromboxanes and leukotrienes. Most of the arachidonic acid in cells is attached at the 2-position of certain phospholipids, and is released by the action of phospholipase A2. The role of Ca2+ in the secretion of these signal molecules will be discussed in the next section. 

Figure 10. Scheme illustrating the main locations and functional role of H3 receptors in the vessels. H3 receptors coupled with inhibitory G proteins (Gj) occur as prejunctional receptors in the adrenergic varicosities, where they negatively modulate noradrenaline (NA) release. Moreover, their activation in endothelial cells can induce muscle relaxation, by the release of inhibitory factors, such as nitric oxide (NO) and prostacyclin (PGI2). In some districts, excitatory H3 receptors were found in muscle cells and they mediate muscle contraction. MC = mast cell NOS = NO synthase COX = cyclooxygenase. 

Luria MH. Atherosclerosis the importance of HDL cholesterol and prostacyclin a role for niacin therapy. Med Hypotheses 1990 32(l) 21-8. 

Cilostazol has a number of additional indirect effects. Similar to dipyridamole, it enhances the actions of prostacyclin, although it has not been reported to directly increase prostacyclin release, Cilostazol also affects endothelial cells, specifically the release of cytokines, such as monocytic chemoattractant protein-1 (MCP-1), which appears to play an important role in the development and progression of atherosclerotic lesions (24). Cilostazol, like other PDE3 inhibitors, acts as a vasodilator. 

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