Retinoids inhibit primary cynomolgus monkey hepatocyte lipoprotein(a) levels

Elevated plasma lipoprotein(a) [Lp(a)] independently contributes to a variety of vascular diseases; consequentially, factors that modulate its levels are of interest. Since Lp(a) is produced by a disulfide linkage between apolipoprotein(a) [apo(a)] and apolipoproteinB-100 (apoB-100) of low density lipoprotein (LDL) on the hepatocyte surface, modulation of either particle may be useful in lowering Lp(a). Using primary cynomolgus monkey hepatocyte cultures that endogenously express apo(a) and apoB-100, we showed that all-trans (retinol, retinal, retinoic acid) and 9-cis (retinal, retinoic acid) retinoids lower Lp(a) accumulation in the cell media, with the 9-cis derivatives being > 10-fold more potent than the all-trans stereoisomers. Lp(a) Towering was related to decreases in apo(a) and its cognate transcript, but not to apoB-100. These results demonstrate that retinoids lower Lp(a) levels by decreasing apo(a) through its cognate mRNA.