Opposite effects of native and oxidized lipoproteins on the activity of secretory phospholipase A2 group IIA

Elevated circulating level and activity of secretory phospholipase A2 group IIA (sPLA2(IIA)) are associated with the development of adverse cardiovascular events. The mechanisms of sPLA2(IIA) activity regulation in human blood serum so far remain obscure. We have suggested that the enzyme activity is influenced by circulating lipoproteins. The activity of sPLA2(IIA) was examined in whole serum of healthy individuals and after removal of lipoproteins from it. The effects of different classes of native and oxidized lipoproteins on sPLA2(IIA) in blood serum were compared with their effects on purified sPLA2(IIA). Activity of sPLA2(IIA) was not detected in whole serum despite the high concentration of the enzyme. However after lipoproteins had been removed from the serum, the lipoprotein-depleted serum displayed sPLA2(IIA) activity which was proportional to the amount of sPLA2(IIA) in it. Native LDL, HDL and VLDL + IDL inhibited the activity of both purified sPLA2(IIA) and the enzyme activity in lipoprotein-depleted serum. By contrast, oxidized LDL, HDL and VLDL + IDL significantly stimulated the activity of purified and serum sPLA2(IIA) and enhanced the release of fatty acids from the substrate. The data indicate that native and oxidized lipoproteins regulate catalytic activity of sPLA2(IIA). Activation of sPLA2(IIA) by oxidized lipoproteins may be regarded as one of the mechanisms of atherosclerosis development.