Isoprostanes: are they more than physiopathological biomarkers of lipid peroxidation?

Biomarkers of Lipid Peroxidation? To the Editor: Isoprostanes are currently used as biomarkers of lipid peroxidation in humans.1 Minuz et al2 recently showed that urinary levels of 15-F2t-IsoP were increased in hypertensive patients suffering from renovascular disease, confirming the experimental data showing that renovascular hypertension and activation of the renin-angiotensin system in general is associated with an increased lipid peroxidation. Conversely, data obtained from 25 patients with essential hypertension showed that urinary levels of 15-F2t-IsoP were not significantly different in comparison with controls. Similarly, we showed that the urinary levels of 15-F2t-IsoP were not increased in untreated patients with mild-tomoderate hypertension.3 In our study, the mean systolic and diastolic blood pressure was similar to Minuz’s essential hypertensive patients, but because our patients were never treated, their hypertension was probably less severe. Both studies are consistent with the hypothesis that oxidative stress is not increased in the early stages of human essential hypertension. However, they do not rule out the possibility that essential hypertension is associated with an increased oxidative stress at later stages, as a consequence of hypertension. A large number of studies show that isoprostane levels are increased in cigarette smokers, homocystinemia, diabetes mellitus, and hypercholesterolemia.4 We now have evidence that renovascular, but not essential, hypertension is associated with increased F2-isoprostane levels. It is likely that the increased levels observed are related to an increased production of these compounds rather than a variation of their clearance. There is no doubt that isoprostanes are key biomarkers to investigate the role of free radical generation in the pathogenesis of human disorders. However, are they more than physiopathological biomarkers? Two fields of investigation remain unknown. Firstly, F2isoprostanes are biologically active. They mediate vasoconstriction in conductance arteries as well as resistance microvessels, and vascular smooth muscle cells mitogenesis. Whether isoprostanes are involved in cardiovascular physiology and pathogenesis remains to be investigated. Secondly, F2-isoprostane levels correlate with disease severity indexes in diseases such as cardiac failure or pulmonary hypertension. Could F2-isoprostane quantification provide prognostic information in such diseases? In other words, does increased lipid peroxidation, similar to inflammation, represent a marker of increased risk of major cardiovascular events in such patients, and could F2-isoprostane represent a prognostic biomarker similar to high-sensitivity C-reactive protein? There is today no evidence that they do. The study of Minuz provides important data concerning the formation of F2-isoprostanes in hypertension. Whether these compounds are more than physiopathological biomarkers of lipid peroxidation needs now to be further investigated.