Verapamil Increases the Apolipoprotein-Mediated Release of Cellular Cholesterol by Induction of ABCA1 Expression Via Liver X Receptor-Independent Mechanism

Shogo Suzuki, Tomoko Nishimaki-Mogami, Norimasa Tamehiro, Kazuhide Inoue, Reijiro Arakawa, Sumiko Abe-Dohmae, Arowu R. Tanaka, Kazumitsu Ueda, Shinji Yokoyama

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

Objective-Release of cellular cholesterol and phospholipid mediated by helical apolipoprotein and ATP-binding cassette transporter (ABC) A1 is a major source of plasma HDL. We investigated the effect of calcium channel blockers on this reaction. Methods and Results-Expression of ABCA1, apoA-I-mediated cellular lipid release, and HDL production were enhanced in cAMP analogue-treated RAW264 cells by verapamil, and similar effects were also observed with other calcium channel blockers. The verapamil treatment resulted in rapid increase in ABCA1 protein and its mRNA, but not the ABCG1 mRNA, another target gene product of the nuclear receptor liver X receptor (LXR). By using the cells transfected with a mouse ABCA1 promoter-luciferase construct (-1238 to +57bp), verapamil was shown to enhance the transcriptional activity. However, it did not increase transcription of LXR response element-driven luciferase vector. Conclusions-The data demonstrated that verapamil increases ABCA1 expression through LXR-independent mechanism and thereby increases apoA-I-mediated cellular lipid release and production of HDL.

Original languageEnglish
Pages (from-to)519-525
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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