Vascular biology of the isoprostanes

Abstract

Isoprostanes are a family of compounds produced from polyunsaturated fatty acids via a free-radical-catalysed mechanism. F(2)-isoprostanes are prostaglandin F(2alpha) isomers derived from arachidonic acid. These compounds induce potent vasoconstriction, mediated primarily by TP receptor stimulation, and in some vessels by the release of cyclooxygenase products. This vasoconstriction may be modulated by the endothelium through the release of NO. Potent vasoconstriction is also observed with E(2)-isoprostanes. Experimental and clinical data suggest a role for F(2)-isoprostanes in atherogenesis. These compounds can be detected in free forms in biological fluids as well as esterified in low-density lipoproteins or cell membranes. Their quantification represents a reliable marker of lipid peroxidation. Elevated levels of F(2)-isoprostanes in biological fluids in pathological conditions including atherosclerosis, ischaemia-reperfusion injury, and inflammatory vascular diseases, suggest a relationship between lipid peroxidation and such diseases. F(2)-isoprostanes are currently being investigated as non-invasive quantitative markers to monitor the response to anti-oxidant treatment.