Microvascular Responses to Eicosanoids

Mauro Perretti and Derek W. Gilroy

The William Harvey Research Institute, Bart s and the London, Queen Mary University of London,

London, United Kingdom

Eicosanoids are low-molecular-weight lipid molecules rapidly generated during normal cell hemostasis or, more often, after cell activation and in conditions of stress. The fact that their generation is rapid indicates their important function in promoting immediate alterations in cell plasticity, thus allowing rapid adaptation to new environments. In more specific terms, eicosanoids are produced following activation of cells that play a central role in modulating microvascular responses (endothelial cells, macrophages and other myeloid cells, fibroblasts, and so on), thereby having a marked impact on a series of microvascular events that characterize several experimental and clinical cardiovascular inflammatory conditions. In this review we will document the various effects eicosanoids have on the microvasculature in terms of cell trafficking, vascular tone, and edema formation.

other hand, catalyze the metabolism of AA to unstable hydroperoxy intermediates that subsequently form the LTs, hydroxyeicosatetraenoic acid, and lipoxins (LXs). AA metabolism by the cytochrome P450 monooxygenase system gives rise to the less characterized EETs.

Eicosanoids have generated enormous interest mainly because of their ubiquity and pleiotropy of biological activities, which affect not only pharmacology but also physiological and pathophysiological events. For instance, it is the inhibition of prostaglandin formation that accounts, at least in part, for the pharmacological mode of action of non-steroidal anti-inflammatory drugs, one of the most widely used families of drugs for the treatment of inflammatory mediated diseases, pain, and control of vascular tone. The use of these drugs and careful analysis of their effects have shed light on previously unappreciated pathophysiological pathways that operate during inflammation.

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