Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases

Arachidonic acid is an essential unsaturated fatty acid and is the most abundant in cell membranes. Its metabolism leads to the formation of the well known prostaglandins and thromboxanes, which are implicated in the modulation of vascular tone and growth and play an important role on the blood-vessel interface. The discovery of their pharmacological activity led to the development of some potent drugs such as the prostacyclin analogues, while thromboxane A2-receptor antagonists are currently under development. While research on arachidonic acid metabolites focused for decades on the enzymatic pathway, Morrow and Roberts 1 described in 1990 another pathway of arachidonic acid metabolism, i.e., a free radical pathway, leading to a large series of compounds termed isoprostanes.A first level of complexity is that, unlike the enzymatic formation of prostaglandins, F2-isoprostanes derive from a non-specific free radical attack of arachidonic acid, i.e., that four different series of compounds, called regioisomers, differing in the nature of their side chains, are formed (Fig. 1). The second level of complexity is that eight isomers may be formed among each of these four regioisomers, i.e., 64 different F2-isoprostanes are formed. The third level of complexity is man-made: three different nomenclatures co-exist2. Given the potential number of compounds, this can lead to a nightmare for the non-specialist, and a puzzle for novices to determine which is which. For clarity, the nomenclature validated by the International Union of Pure and Applied Chemistry3 should be used. The fourth level of complexity is that F2-isoprostanes are only one family of the myriad of compounds produced through free radical peroxidation of …