Abstract
We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(∼10 mg/dl; range 10-11 mg/dl), intermediate (∼50 mg/dl; range 30-61 mg/dl), or high (>100 mg/dl; range 78-128 mg/dl) Lp(a) levels. By using enzymatic and immunoassays, the content of OxPL and Lp-PLA(2) mass and activity were quantitated in lipoprotein density fractions plated in microtiter wells, as well as directly on apoB-100, Lp(a), and apoA-I immunocaptured within each fraction (i.e., OxPL/apoB and Lp-PLA(2)/apoB). In whole fractions, OxPL was primarily detected in the Lp(a)-containing fractions, whereas Lp-PLA(2) was primarily detected in the small, dense LDL and light Lp(a) range. In lipoprotein capture assays, OxPL/apoB and OxPL/apo(a) increased proportionally with increasing Lp(a) levels. Lp-PLA(2)/apoB and Lp-PLA(2)/apoA-I levels were highest in the low Lp(a) group but decreased proportionally with increasing Lp(a) levels. Lp-PLA(2)/apo(a) was lowest in patients with low Lp(a) levels and increased proportionally with increasing Lp(a) levels. Apheresis significantly reduced levels of OxPL and Lp-PLA(2) on apoB and Lp(a) (50-75%), particularly in patients with intermediate and high Lp(a) levels. In contrast, apheresis increased Lp-PLA(2)-specific activity (activity/mass ratio) in buoyant LDL fractions. The impact of apheresis on Lp(a), OxPL, and Lp-PLA(2) provides insights into its therapeutic benefits beyond lowering apoB-containing lipoproteins.
Highlights
We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A2 (Lp-PLA2) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(ف10 mg/dl; range 10–11 mg/dl), intermediate (ف50 mg/dl; range 30–61 mg/dl), or high (>100 mg/dl; range 78–128 mg/dl) Lp(a) levels
Plasma levels of OxPL on apoB-100 (OxPL/apoB), detected by monoclonal antibody E06, are elevated in subjects with coronary artery disease (CAD) and predict the presence and progression of carotid and femoral atherosclerosis and higher risk of future death, myocardial infarction, and stroke. They enhance the predictive value of the Framingham Risk Score and increase the area under the curve using c-index statistics, reflecting its Abbreviations: CAD, coronary artery disease; CVD, cardiovascular disease; FH, familial hypercholesterolemia; HDL-C, HDL-cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, LDL-cholesterol; Lp(a), lipoprotein (a); Lp-PLA2, lipoprotein-associated phospholipase
Apheresis significantly reduced levels of proatherogenic and proinflammatory OxPL and Lp-PLA2 on apoB and Lp(a), in patients with high Lp(a) levels, while increasing Lp-PLA2-specific activity in buoyant LDL particles. These data provide a scientific rationale for understanding how apheresis may provide clinical benefits beyond lowering apoB-containing lipoproteins [26] and in understanding the pathophysiological relationships among Lp(a), OxPL, and Lp-PLA2 in collectively mediating CVD [5, 6, 9]
Summary
We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A2 (Lp-PLA2) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(ف10 mg/dl; range 10–11 mg/dl), intermediate (ف50 mg/dl; range 30–61 mg/dl), or high (>100 mg/dl; range 78–128 mg/dl) Lp(a) levels. Plasma levels of OxPL on apoB-100 (OxPL/apoB), detected by monoclonal antibody E06, are elevated in subjects with coronary artery disease (CAD) and predict the presence and progression of carotid and femoral atherosclerosis and higher risk of future death, myocardial infarction, and stroke (reviewed in Ref. 3) They enhance the predictive value of the Framingham Risk Score and increase the area under the curve using c-index statistics, reflecting its Abbreviations: CAD, coronary artery disease; CVD, cardiovascular disease; FH, familial hypercholesterolemia; HDL-C, HDL-cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, LDL-cholesterol; Lp(a), lipoprotein (a); Lp-PLA2, lipoprotein-associated phospholipase Orsoni contributed to this work. 3 To whom correspondence should be addressed
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