Prostanoids actions in cardiovascular physiopathology

Abstract

Prostaglandins (PGs) and thromboxanes (TXs) play a pivotal role in cardiovascular physiopathology. They are synthesized from arachidonic acid by the enzymatic action of cyclooxygenases (COXs), leading to the production of an unstable intermediate, PGH2 that is subsequently converted to the different prostaglandins and thromboxanes (PGE2, PGD2, PGI2, PGF2á and TXA2) by the action of different synthases and isomerases. There are two well characterized COX enzymes, termed COX-1 and COX-2, with different properties. While COX-1 is expressed constitutively in most tissues and is thought to be involved in homeostatic prostanoid biosynthesis, COX-2 is transcriptionally up-regulated in response to mitogens and pro-inflammatory stimuli being the predominant isoform involved in the inflammatory response. In the cardiovascular system, prostanoids have been shown to modulate the pathogenesis of vascular diseases as thrombosis and atherosclerosis through a variety of processes, including platelet aggregation, vasorelaxation and vasoconstriction, local inflammatory response and leukocyte-endothelial cell adhesion. Multiple studies using pharmacological inhibitors and genetically deficient mice have demonstrated the importance of prostanoid-mediated actions on cardiovascular physiology. However, recent withdrawal of COX-2 selective inhibitors from the clinic because of their adverse effects in patients with potential cardiovascular risk has opened a debate about the role of COX�derived prostanoids in vascular pathologies and the benefits and risks for the use of COX inhibitors in cardiovascular diseases