Acute effects of low density lipoprotein apheresis on metabolic parameters of apolipoprotein B.
Apheresis is a treatment option for patients with severe hypercholesterolemia and coronary artery disease. It is unknown whether such therapy changes kinetic parameters of lipoprotein metabolism, such as apolipoprotein B (apoB) secretion rates, conversion rates, and fractional catabolic rates (FCR). We studied the acute effect of apheresis on metabolic parameters of apoB in five patients with drug-resistant hyperlipoproteinemia, using endogenous labeling with D(3)-leucine, mass spectrometry, and multicompartmental modeling. Patients were studied prior to and immediately after apheresis therapy. The two tracer studies were modeled simultaneously, taking into account the non-steady-state concentrations of apoB. The low density lipoprotein (LDL)-apoB concentration was 120+/-32 mg dl(-1) prior to and 52+/-18 mg dl(-1) immediately after apheresis therapy. The metabolic studies indicate that no change in apoB secretion (13.9+/- 4.9 mg kg(-1) day(-1)) is required to fit the tracer and apoB mass data obtained before and after apheresis and that in four of the five patients the LDL-apoB FCR (0.21+/-0.02 day(-1)) was not altered after apheresis. In one subject the LDL-apoB FCR temporarily increased from 0.22 day(-1) to 0.35 day(-1) after apheresis. The conversion rate of very low density lipoprotein (VLDL)-apoB to LDL-apoB is temporarily decreased from 76 to 51% after apheresis and thus less LDL-apoB is produced after apheresis. We conclude that an acute reduction of LDL-apoB concentration does not affect apoB secretion or LDL-apoB FCR, but that apoB conversion to LDL is temporarily decreased. Thus, in most patients the decreased rate of delivery of neutral lipids or apoB to the liver does not result in an upregulation of LDL receptors or in decreased apoB secretion.
Parhofer
K G
KG
Department of Internal Medicine II, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
Barrett
P H
PH
Demant
T
T
Schwandt
P
P
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood* / Q000172:deficiency; D001781:Blood Component Removal / Q000009:adverse effects*; D003327:Coronary Disease / Q000097:blood; D003903:Deuterium; D004351:Drug Resistance; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D003903:Deuterium; D007930:Leucine