The putative role of isoprostanes in human cardiovascular physiology and disease: following the fingerprints.

Isoprostanes are arachidonic acid metabolites produced through a free radical dependent mechanism. They are formed in situ on phospholipids, at sites of free radical generation. Once released from cell membranes by phospholipases, isoprostanes circulate in the plasma in free form, and are potentially available for agonist receptor interaction. Increased formation of isoprostanes was first described in cigarette smokers. Since this study, their increased formation has been observed in a large number of diseases including atherosclerosis and coronary heart disease. Some reports also showed that isoprostanes concentrations were increased in the pericardial fluid and urine of patients suffering from heart failure. Isoprostane concentrations increased with the functional severity of heart failure. The study by NonakaSarukawa and colleagues in this issue of Heart further supports the hypothesis that oxidative stress, assessed by urinary 15-F2t-isoprostane concentrations, is increased in patients with congestive heart failure and correlates with the severity of the disease. They showed that 15-F2t-isoprostane values decreased in the 14 days following hospital admission. Interestingly, 15-F2t-isoprostane values were correlated with plasma B type natriuretic peptide (BNP). These data raise an important issue: in addition to being a pathophysiological marker of oxidative injury, the quantification of F2-isoprostanes might represent a prognostic marker in heart failure—that is, a marker of morbidity, as suggested by the authors. However, no clinical studies aimed at testing isoprostanes as a prognostic marker, with strong end points such as mortality or morbidity, are available in heart failure as well as other cardiovascular diseases.