Isoprostanes and other markers of peroxidation in atherosclerosis

Several lines of evidence suggest that reactive oxygen species play a role in the development of vasculopathies, including those that define atherosclerosis, hypertension and restenosis after angioplasty. Confused picture emerging from prospective clinical trials of anti-oxidants may reflect inadequacy of traditional indices of lipid peroxidation in the recruitment of appropriate patients and in guiding the selection of the appropriate dose of anti-oxidant to be tested. Ex vivo indices of oxidant stress could have questionable veracity in assessing the actual rate of lipid peroxidation in vivo. The measurement of F-2-isoprostanes (F-2-iPS), formed non-enzimatically through free radical catalysed attack on esterified arachidonate, provides a reliable tool for identifyng populations with enhanced rates of lipid peroxidation. Enhanced formation of F-2-iPS, together with increased in vivo platelet activation, has been reported in association with several cardiovascular risk factors. Thus, it has been suggested that F-2-iPS may transduce oxidant stress-dependent platelet activation. Measurements of 8-iso-PGF(2 alpha), an abundant F-2-iP formed in vivo, in urine may provide sensitive biochemical end-points for the assessment of the oxidant status of the patient and the true efficacy of anti-oxidant therapies. The incorporation of such biochemical end-points in clinical trials may help to verify the reliability of the oxidative modification hypothesis in the development of atherosclerosis.