title: An in vitro system for identifying agents capable of changing serum lipoprotein(a) concentration by regulating the transcriptional activity of the apolipoprotein(a) gene promoter.
abstract: A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and independent risk factor for cardiovascular disease. We examined the effects of agents on the transcriptional activity of the apolipoprotein(a) [apo(a)] gene promoter and determined whether drugs identified by this assay would affect the serum concentration of Lp(a) in vivo. All-trans-retinoic acid (ATRA) and interleukin-6 increased the transcriptional activity of the apo(a) gene promoter 2.1- and 2.5-fold, respectively, 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, respectively. Thus, the in vitro luciferase assay system is capable of identifying agents that affect the serum concentration of Lp(a) and thus may prove beneficial in the screening of new drugs for treatment of individuals with high serum Lp(a) concentrations.
authors.affiliation: First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Azuma
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Mima
authors.forename: M
authors.initials: M
authors.lastname: Shirakawa
authors.forename: K
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kanagawa
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Shigekiyo
authors.forename: S
authors.initials: S
authors.lastname: Saito
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics*; D053241:Apoprotein(a); D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000097:blood; D017931:DNA Primers; D003613:Danazol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D018197:Hepatoblastoma; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood*; D008113:Liver Neoplasms; D008156:Luciferases / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D001053:Apolipoproteins; D017931:DNA Primers; D015850:Interleukin-6; D017270:Lipoprotein(a); D011993:Recombinant Fusion Proteins; D014284:Triiodothyronine; D014810:Vitamin E; D014212:Tretinoin; D004247:DNA; D008156:Luciferases; D053241:Apoprotein(a); D003613:Danazol