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 identifying 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(2alpha), 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.
Patrignani
Paola
P
Department of Medicine and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy. ppatrignani@unich.it
Tacconelli
Stefania
S
D017130:Angioplasty; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology*; D015415:Biomarkers; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism*; D015227:Lipid Peroxidation; D016877:Oxidants / Q000737:chemistry; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D015539:Platelet Activation; D017382:Reactive Oxygen Species
D000975:Antioxidants; D015415:Biomarkers; D028421:Isoprostanes; D016877:Oxidants; D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D010100:Oxygen