On the present and future role of Lp-PLA2 in atherosclerosis-related cardiovascular risk prediction and management

Abstract

Circulating concentration and activity of secretory phospholipase A<SUB>2</SUB> (sPLA<SUB>2</SUB>) and lipoprotein-associated phospholipase A<SUB>2</SUB> (Lp-PLA<SUB>2</SUB>) have been proven as biomarkers of increased risk of atherosclerosis-related cardiovascular disease (ASCVD). Lp-PLA<SUB>2</SUB> might be part of the atherosclerotic process and may contribute to plaque destabilisation through inflammatory activity within atherosclerotic lesions. However, all attempts to translate the inhibition of phospholipase into clinically beneficial ASCVD risk reduction, including in randomised studies, by either non-specific inhibition of sPLA<SUB>2</SUB> (by varespladib) or specific Lp-PLA<SUB>2</SUB> inhibition by darapladib, unexpectedly failed. This gives us a strong imperative to continue research aimed at a better understanding of how Lp-PLA<SUB>2</SUB> and sPLA<SUB>2</SUB> regulate vascular inflammation and atherosclerotic plaque development. From the clinical viewpoint there is a need to establish and validate the existing and emerging novel anti-inflammatory therapeutic strategies to fight against ASCVD development, by using potentially better animal models and differently designed clinical trials in humans.