Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
Original Articles
Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPARγ
Kazuhiro NakayaMakoto AyaoriTetsuya HisadaShojiro SawadaNobukiyo TanakaNoriyuki IwamotoMasatsune OguraEmi YakushijiMasatoshi KusuharaHaruo NakamuraFumitaka Ohsuzu
Author information
Keywords: ARB, PPARγ, LXR
JOURNALS FREE ACCESS

Volume 14 (2007) Issue 3 Pages 133-141

Details
Download PDF (286K) Contact us
Abstract

Aim: The ATP binding cassette transporters A1 and G1 (ABCA1/G1) and scavenger receptor class B type I (SR-BI) are key molecules in cholesterol efflux and atherogenesis. These genes are regulated by peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor (LXR). Telmisartan is an angiotensin type 1 receptor blocker which has been reported to act as a ligand for PPARγ. We investigated whether PPARγ-activating ARBs affect the expression of these genes and cholesterol efflux from macrophages.
Methods and Results: Telmisartan increased ABCA1, ABCG1 and SR-BI mRNA levels in THP-1 macrophages in a dose- and time-dependent fashion. It also increased their protein levels and enhanced apoA-I- and HDL-mediated cholesterol efflux from macrophages. The knockdown of PPARγ by siRNA abolished the telmisartan-induced expression of these genes. The knockdown of LXRα resulted in the complete and partial abolishment of telmisartan-induced ABCA1 and ABCG1 expression, respectively. We also demonstrated that telmisartan-induced SR-BI expression was dependent on the PPARγ pathway but not on the LXRα pathway. A luciferase assay using an ABCA1 promoter construct showed that telmisartan activated ABCA1 transcription, which was abolished if the LXR binding element was mutated, indicating that increased ABCA1 transcription by telmisartan is LXR-dependent.
Conclusion: Our results showed that telmisartan enhanced both apoA-I- and HDL-mediated cholesterol efflux from macrophages by increasing ABCA1, ABCG1 and SR-BI expression via PPARγ-dependent and LXR-dependent/independent pathways.

Information related to the author
Previous article Next article

Recently visited articles
feedback
Top