Tselepis_2010_J.Lipid.Res_51_3331

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent cardiovascular risk factor. We investigated the plasma levels of Lp-PLA(2) activity and mass as a function of plasma lipid levels, LDL subclass profile, and oxidative stress in patients with beta-thalassemia. Thirty-five patients with beta-thalassemia major (beta-TM) and 25 patients with beta-thalassemia intermedia (beta-TI) participated in the study. Lp-PLA(2) activity and mass were measured in total plasma, in apolipoprotein (apo)B-depleted plasma (HDL-Lp-PLA(2)), and in LDL subclasses. Lp-PLA(2) activity produced and secreted from peripheral blood monocytes in culture was also determined. Patients with beta-thalassemia are characterized by a predominance of small-dense LDL particles, increased oxidative stress, and very high plasma levels of Lp-PLA(2) mass and activity, despite low LDL-cholesterol levels. A significant positive correlation between plasma Lp-PLA(2) activity or mass and 8-isoprostane (8-epiPGF2a) and ferritin levels as well as intima-media thickness (IMT) values was observed. An increase in secreted and cell-associated Lp-PLA(2) activity from monocytes in culture was observed in both patient groups. The HDL-Lp-PLA(2) activity and mass as well as the ratio of HDL-Lp-PLA(2)/plasma Lp-PLA(2) were significantly higher in both patient groups compared with the control group. In conclusion, patients with beta-thalassemia exhibit high plasma Lp-PLA(2) levels, attributed to increased enzyme secretion from monocytes/macrophages and to the predominance of sdLDL particles in plasma. Plasma Lp-PLA(2) is correlated with carotid IMT, suggesting that this enzyme may be implicated in premature carotid atherosclerosis observed in beta-thalassemia.