Abstract 14163: Oxidized Phospholipids and Lipoprotein-Associated Phospholipase A2 in Plasma, ApoB-containing and ApoAI -containing Lipoprotein Subfractions in Patients with Familial Hypercholesterolemia: Effect of LDL Apheresis
Objectives: Lp(a) is a causal, genetic risk factor for cardiovascular disease (CVD) and is enriched in pro-inflammatory oxidized phospholipids (OxPL) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Epidemiologic outcomes studies have shown that the OxPL, Lp(a) and Lp-PLA2 collectively mediate additive risk for CVD. To derive new insights into these findings, we evaluated the impact of apheresis on lipoprotein-associated OxPL and Lp-PLA2 mass in pts with familial hypercholesterolemia (FH).
Methods: Patients with FH (n=18) on chronic LDL apheresis were divided into three groups according to low (<10mg/dl), intermediate (∼50mg/dl) and high (100mg/dl<) plasma Lp(a) levels measured pre-apheresis. Lipoprotein subfractions (n=25 from each patient pre- and post-apheresis) were isolated by isopycnic density gradient fractionation. OxPL were measured with antibody E06 and Lp-PLA2 with antibody 4B4 directly in whole plasma and in derived subfractions. Additionally, OxPL and Lp-PLA2 content in isolated lipoproteins [apoB-100, Lp(a) and apoA1] was determined using specific capture antibodies on microtiter well plates pre- and post-apheresis.
Results: In plasma and subfractions, OxPL were present primarily on Lp(a), but minimally on non-Lp(a)-apoB or apoAI. OxPL were almost exclusively detected in density 1.059-1.094 g/ml where Lp(a) is prevalent and in proportion to the amount of Lp(a) present. In plasma and subfractions, Lp-PLA2 was present primarily on apoB particles; however the proportion of Lp-PLA2 decreased in apoB-containing subfractions but progressively increased in Lp(a) as Lp(a) plasma levels increased. LDL apheresis resulted in significant reductions of OxPL and Lp-PLA2 in plasma, in apoB-containing subfractions and on isolated apoB and Lp(a).
Conclusions: By physical separation and immunological techniques, OxPL are primarily present on the Lp(a) particle. Lp-PLA2 is present primarily on apoB-containing particles but the proportion on Lp(a) increases as plasma Lp(a) levels increase. These data suggest that Lp(a), OxPL and Lp-PLA2 are pathophysiologically linked, particularly as Lp(a) levels increase, and provide a rationale for understanding their interactive role in mediating atherothrombosis and CVD in humans.
- © 2010 by American Heart Association, Inc.