Aspirin reduces apolipoprotein(a) (Apo(a)) production in human hepatocytesby suppression of apo(a) gene transcription

Citation
A. Kagawa et al., Aspirin reduces apolipoprotein(a) (Apo(a)) production in human hepatocytesby suppression of apo(a) gene transcription, J BIOL CHEM, 274(48), 1999, pp. 34111-34115
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
274
Issue
48
Year of publication
1999
Pages
34111 - 34115
Database
ISI
SICI code
0021-9258(19991126)274:48<34111:ARA(PI>2.0.ZU;2-9
Abstract
High serum lipoprotein(a) (Lp(a)) is a risk factor for vascular disorders, Our preliminary observations suggest that, in some patients with coronary h eart disease with high serum Lp(a) levels, administration of aspirin reduce d Lp(a) levels. Therefore, we aimed to analyze the effects of aspirin on th e production of apo(a), the expression of apolipoprotein(a) (apo(a)) mRNA a nd the transcriptional activity of apo(a) gene promoter. Aspirin (5 mM) red uced the apo(a) levels in culture medium of human hepatocytes and suppresse d apo(a) mRNA expression to 73% and 85% of the controls, respectively. Aspi rin also reduced the transcriptional activity of apo(a) gene transfected in to HepG2 hepatoma cells in a dose-dependent manner, with a maximal effect a t 5 mM (44.3 +/- 1.5% of the control). Sodium salicylate (5 mM) also reduce d apo(a) gene transcription, whereas indomethacin (10 mu M) had no effect. Deletion analysis of apo(a) gene promoter showed that promoter region exten ding from -30 to +138 is critical for the effect of aspirin, Furthermore, e nhanced production, mRNA expression, and gene transcription of apo(a) by in terleukin-6 were also inhibited by aspirin. These results demonstrate that aspirin reduces apo(a) production from hepatocytes via reduction of the tra nscriptional activity of apo(a) gene with suppression of apo(a) mRNA expres sion. The suppression of apo(a) production by aspirin may at least in part play a role in the anti-atherogenic effect of aspirin in vascular disorders .