Abdominal aortic aneurysm (AAA) is a late-age onset disorder that affects a high percentage of the population in industrialized countries, and rupture of AAA is associated with high mortality rates ( 1 ). The etiology of AAA is complex with a relevant contribution of genetic factors ( 2 ). Although much effort has been made to clarify the mechanism of AAA development, currently the only effective approach to prevent aneurysm rupture is surgical repair by conventional or endovascular techniques.Evidence has been established for a relationship between atherosclerosis and AAA, both disorders being characterized by an underlying chronic infl ammation . However, there are marked differences between atherosclerotic lesions and AAA. Whereas atherosclerotic plaque is characterized by leukocyte infi ltration at the lumen site and hyperproliferation of vascular smooth muscle cells (VSMCs) causing neointimal hyperplasia, AAA is characterized by leukocyte infi ltration into adventitia and depletion of VSMCs in the media. Other relevant features of AAA are the wall tension strength breakdown caused by proteolytic enzymes progressively destructing elastic fi bers ( 3 ) and hypervascularization of aortic tissue. It has been proposed that this vascularization might contribute to the development and rupture of aneurysms ( 4, 5 ). Abstract We investigated the prostaglandin (PG)E

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cPTIO (2-[4-carboxyphenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) exerts beneficial actions on systemic inflammatory response. Besides its nitric oxide (NO) scavenging properties cPTIO could exert beneficial effects through modulation of arachidonic acid metabolism. We studied the effect of cPTIO on the biosynthesis of vasoactive prostaglandins (PG) by endothelial cells. Human cord umbilical vein endothelial cells (HUVEC) were treated with cPTIO, and expression of cycloxygenase (COX) isoenzymes in terms of mRNA and protein was determined by real-time-PCR and immunoblotting. Release of PGE2 (as index of untransformed PGH2 release) and 6-oxo-PGF1alpha (PGI2 stable metabolite) was determined by enzyme-immunoassay. cPTIO significantly increases the release of untransformed PGH2 associated to the induction of COX-2 expression. Experiments with NO-synthase inhibitors and radical scavengers showed that induction of COX-2 by cPTIO was mediated by free radical species, likely caused by the mobilization of NO from cellular stores. Finally, using specific signal-transduction inhibitors we show the involvement of Src/PI3-K/PKC pathway. Additional effects other than a direct NO scavenging activity may confer therapeutic advantages to cPTIO as compared with NO-synthase inhibitors for the treatment of systemic inflammation-associated vascular hyporeactivity.