J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol 34, 1975-1982, Copyright © 1993 by Lipid Research, Inc.

ARTICLES

Lovastatin enhances hepatic uptake of low density lipoprotein in humans

K Kervinen, MJ Savolainen, JI Heikkila and YA Kesaniemi
Department of Internal Medicine, University of Oulu, Finland.

A noninvasive method for visualizing the uptake of low density lipoprotein (LDL) was used to investigate the effect of hypolipidemic drugs on LDL uptake by the human liver in vivo. Fourteen hypercholesterolemic patients (six with familial hypercholesterolemia and eight with common hypercholesterolemia) were studied. Autologous LDL particles were isolated and divided into two aliquots; one was labeled with 99mTC and the other with 131I, and both preparations were reinjected simultaneously. The labeled LDL was visualized 24 h later by scanning the thorax and abdomen with a gamma camera, and the liver/heart ratio was calculated as an estimate of the hepatic uptake of LDL. The results of 99mTC-labeled LDL scintigraphy were compared with conventional determinations of the fractional catabolic rate (FCR) for 131I-labeled LDL. The latter correlated best with the liver/heart ratio (r = 0.80, P < 0.001). Lovastatin treatment increased the liver/heart ratio (15%, P < 0.01) in the patients with polygenic hypercholesterolemia and the FCR for LDL in both groups (22%, P < 0.05, for those with familial hypercholesterolemia and 37%, P < 0.01 for those with polygenic hypercholesterolemia). Scanning of the liver using the 99mTC-labeled LDL method provides a noninvasive method for visualizing the hepatic uptake of LDL in vivo in humans. This study also provides direct proof that lovastatin, a drug that enhances LDL receptor activity in the liver, also increases the hepatic uptake of LDL in humans.
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