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Am J Physiol Lung Cell Mol Physiol (September 26, 2008). doi:10.1152/ajplung.90394.2008
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Submitted on July 23, 2008
Revised on September 4, 2008
Accepted on September 22, 2008

LXR-INDUCED REVERSE CHOLESTEROL TRANSPORT IN HUMAN AIRWAY SMOOTH MUSCLE IS MEDIATED EXCLUSIVELY BY ABCA1

Christopher J. Delvecchio1, Patricia Bilan1, Parameswaran Nair2, and John P. Capone1*

1 McMaster University
2 St. Joseph's Healthcare

* To whom correspondence should be addressed. E-mail: caponej{at}mcmaster.ca.

The association of hypercholesterolemia and obesity with airway hyper-responsiveness has drawn increasing attention to the potential role of cholesterol and lipid homeostasis in lung physiology and in chronic pulmonary diseases such as asthma. We have recently shown that activation of the nuclear hormone receptor liver-X-receptor (LXR) stimulates cholesterol efflux in human airway smooth muscle (hASM) cells and induces expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, members of a family of proteins that mediate reverse cholesterol and phospholipid transport. We show here that ABCA1 is responsible for all LXR-mediated cholesterol and phospholipid efflux to both apolipoprotein AI and high density lipoprotein acceptors. In contrast, ABCG1 does not appear to be required for this process. Moreover, we show that hASM cells respond to increased levels of cholesterol by inducing expression of ABCA1 and ABCG1 transporters, a process that is dependent on LXR expression. These findings establish a critical role for ABCA1 in reverse cholesterol and phospholipid transport in ASM cells, and suggest that dysregulation of cholesterol homeostasis in these cells may be important in the pathogenesis of diseases such as asthma.




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