Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia.
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.
Tokyo Women's University, Tokyo,  Japan.
Kiyohito
K
Arai
Alexina
A
Orsoni
Ziad
Z
Mallat
Alain
A
Tedgui
Joseph L
JL
Witztum
Eric
E
Bruckert
Alexandros D
AD
Tselepis
M John
MJ
Chapman
Sotirios
S
Tsimikas
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000150:complications; D001781:Blood Component Removal; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D054497:Phospholipases A2, Secretory / Q000097:blood; D010743:Phospholipids / Q000097:blood* / Q000378:metabolism*; D012189:Retrospective Studies
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D010743:Phospholipids; D002097:C-Reactive Protein; D054497:Phospholipases A2, Secretory; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase