Ramharack R, Spahr M A, Sekerke C S
Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.
Biochem Biophys Res Commun. 1997 Sep 8;238(1):48-52. doi: 10.1006/bbrc.1997.7240.
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.
血浆脂蛋白(a)[Lp(a)]水平升高会独立导致多种血管疾病；因此，调节其水平的因素备受关注。由于Lp(a)是由肝细胞表面载脂蛋白(a)[apo(a)]与低密度脂蛋白(LDL)的载脂蛋白B-100(apoB-100)通过二硫键连接而成，调节其中任何一种颗粒都可能有助于降低Lp(a)。我们使用内源性表达apo(a)和apoB-100的原代食蟹猴肝细胞培养物，发现全反式（视黄醇、视黄醛、视黄酸）和9-顺式（视黄醛、视黄酸）类视黄醇可降低细胞培养基中Lp(a)的积累，其中9-顺式衍生物的效力比全反式立体异构体强10倍以上。Lp(a)水平降低与apo(a)及其同源转录本的减少有关，但与apoB-100无关。这些结果表明，类视黄醇通过其同源mRNA降低apo(a)水平，从而降低Lp(a)水平。
