Increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia

Abstract

The regulation of cellular LDL metabolism by hypertriglyceridemic LDL was tested before and after treatment with acipimox, a nicotinic acid derivative, in 11 type IV hyperlipidemic patients. Large, less dense LDL particles were found in plasma after acipimox treatment. HDL subfractions were only slightly modified, with an increase of dense, cholesteryl ester-enriched and triglyceride-poor HDL3 particles. The LDL (B, E) receptor activity in human skin fibroblasts of LDL isolated before and after treatment was also evaluated. Hypertriglyceridemic LDL proved rather inefficient in regulating receptor activity, with a close to 30% lower capacity than normal LDL to inhibit receptor-mediated uptake and degradation of 125I-LDL. This abnormality was fully corrected after acipimox. The reported findings indicate that acipimox treatment in type IV patients can normalize the defective interaction of hypertriglyceridemic LDL with the LDL (B, E) receptor.

Effects of acipimox on haemorheology and plasma lipoproteins in patients with mixed hyperlipoproteinaemia

“…The reduced concentration of apolipoprotein B in spite of unchanged LDL cholesterol indicates that acipimox therapy induces a shift from small, dense LDL particles to larger particles as described before [ 27]. These larger, more buoyant LDL particles observed during acipimox therapy were shown to have a higher affinity for the LDL receptor [ 28]. Thus, despite an unchanged LDL cholesterol concentration acipimox therapy results in fewer, less atherogenic particles and thus in an improvement of the risk profile.…”