AN IN-VITRO SYSTEM FOR IDENTIFYING AGENTS CAPABLE OF CHANGING SERUM LIPOPROTEIN(A) CONCENTRATION BY REGULATING THE TRANSCRIPTIONAL ACTIVITYOF THE APOLIPOPROTEIN(A) GENE PROMOTER

A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and independent risk factor for cardiovascular disease. We examined th e effects of agents on the transcriptional activity of the apolipoprot ein(a) [apo(a)] gene promoter and determined whether drugs identified by this assay would affect the serum concentration of Lp(a) in vivo. A ll-trans-retinoic acid (ATRA) and interleukin-6 increased the transcri ptional activity of the apo(a) gene promoter 2.1- and 2.5-fold, respec tively, whereas danazol reduced activity to 76% of the control value. Triiodothyronine had no effect on transcriptional activity. Treatment of two acute promyelocytic leukemia patients with ATRA induced maximal 2.7- and 3.2-fold increases in serum Lp(a) concentrations, respective ly. Thus, the in vitro luciferase assay system is capable of identifyi ng agents that affect the serum concentration of Lp(a) and thus may pr ove beneficial in the screening of new drugs for treatment of individu als with high serum Lp(a) concentrations. (C) 1996 Academic Press, Inc .