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on October 18, 2004

Circulation. 2004
Published online before print October 18, 2004, doi: 10.1161/01.CIR.0000146333.20727.2B
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Submitted on August 19, 2002
Revised on June 3, 2004
Accepted on July 1, 2004

Cellular Physiology of Cholesterol Efflux in Vascular Endothelial Cells

Brian J. O’Connell BA, Maxime Denis MSc, and Jacques Genest MD*

From the Cardiovascular Genetics Laboratory, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.

* To whom correspondence should be addressed. E-mail: jacques.genest{at}muhc.mcgill.ca.

Background--Of the cells that compose the atherosclerotic plaque, vascular endothelial cells are the most resistant to cholesterol accumulation. Cholesterol efflux pathways may play an important role in endothelial cholesterol homeostasis.

Methods and Results--We examined the global genetic response of endothelial cells to cholesterol and in particular the contribution of the cholesterol efflux proteins ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor B-I (SR-BI) to endothelial cell cholesterol efflux. The ABCG1 gene is induced in endothelial cells by cholesterol, whereas ABCA1 is not. Using specific chemical inhibitors of ABC transporters and SR-BI, we have shown that neither ABC transporters nor SR-BI is required for apolipoprotein A-1-mediated endothelial cholesterol efflux.

Conclusions--Endothelial cells may use nontraditional pathways for cholesterol efflux.


Key words: endothelium • cholesterol • genes




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