Prostaglandins and thromboxane A 2 (TXA 2), collectively termed prostanoids, are formed when arachidonic acid (AA), a 20-carbon unsaturated fatty acid, is released from the plasma membrane by phospholipases (PLAs) and metabolized by the sequential actions of prostaglandin G/H synthase, or cyclooxygenase (COX), and respective synthases. In this review, we will discuss the biosynthesis of and response to prostaglandins and the pharmacology of their blockade in orchestrating the inflammatory response, with particular regard to cardiovascular disease. While the pro-inflammatory properties of individual prostaglandins during the acute inflammatory response are well established, their role in the resolution of inflammation is more controversial. Their biosynthesis is significantly increased in inflamed tissue and they contribute to the development of the cardinal signs of acute inflammation. Prostaglandins play a key role in the generation of the inflammatory response. It may be anticipated, therefore, that failure of acute inflammation to resolve may predispose to auto-immunity, chronic dysplastic inflammation and excessive tissue damage ( 1). The usual outcome of the acute inflammatory program is successful resolution and repair of tissue damage, rather than persistence and dysfunction of the inflammatory response, which can lead to scarring and loss of organ function. During the resolution of inflammation, granulocytes are eliminated and macrophages and lymphocytes return to normal pre-inflammatory numbers and phenotypes. Once the initiating noxious stimulus is removed via phagocytosis, the inflammatory reaction can decrease and resolve. This process causes the cardinal signs of acute inflammation: rubor (redness), calor (heat), tumor (swelling) and dolor (pain). The acute phase of inflammation is characterized by the rapid influx of blood granulocytes, typically neutrophils, followed swiftly by monocytes that mature into inflammatory macrophages that subsequently proliferate and thereby affect the functions of resident tissue macrophages. Inflammation is an intrinsically beneficial event that leads to removal of offending factors and restoration of tissue structure and physiological function. Inflammation is the immune system’s response to infection and injury and has been implicated in the pathogeneses of arthritis, cancer and stroke, as well as in neurodegenerative and cardiovascular disease.
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