The biological significance of plasmalogens in defense against oxidative damage

The phospholipid class of plasmalogens is ubiquitously found in considerable amounts as a constituent of mammalian cell membranes and of plasma lipoproteins. Plasmalogens are more susceptible to oxidative reactions compared to their fatty acid ester analogues, due to the reactivity of their enolether function. Studies on plasmalogen-deficient cell lines lead to the proposal that these ether lipids serve as endogenous antioxidants. No clear conclusions regarding the antioxidative effects of plasmalogens could be drawn from studies in patients of different ages with peroxisomal deficiency disorders. A defective peroxisomal plasmalogen synthesis is not necessarily associated with other defects in the metabolism of peroxisomes, as has been established in a cell line recently. In different mammalian tissues a decrease of plasmalogens with age was described. Moreover, an accumulation of plasmalogen oxidation products was measured in brain of old cattle compared to young ones. In pathologic conditions associated with oxidative stress like in spinal cord ischemia and reperfusion, plasmalogen levels varied inversely according to the oxidative burden. Oxidation products of plasmalogens increased with time of ischemia in infarcted porcine heart tissue. Enrichment of lipoproteins with plasmalogens increased their oxidative resistance, which was diminished in the case of LDL particles in patients with coronary arteriosclerosis. In red cell membranes plasmalogens were reduced with donor age and in hyperlipidemia. Under lipid lowering therapy with lovastatin an increase was observed, indicating a possible antioxidative impact of this treatment. Taken together, there is good evidence that plasmalogens are effective as endogenous antioxidants. However, more experimental approaches not confounded by other lipolytic processes are needed to establish this role of plasmalogens.