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A more recent version of this article appeared on February 1, 2004

Papers In Press, published online ahead of print November 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300231-JLR200
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Submitted on May 29, 2003
Revised on September 12, 2003
Accepted on October 29, 2003

In vivo modulation of HDL phospholipid has opposing effects on SR-BI- and ABCA1-mediated cholesterol efflux

Patricia G. Yancey, Masa-aki Kawashiri, Ryan Moore, Jane M. Glick, David L. Williams, Margery A. Connelly, Daniel J. Rader, and George H. Rothblat

GI/Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104

Corresponding Author: rothblat{at}email.chop.edu

The effects of in vivo modulation of HDL phospholipid (PL) on scavenger receptor BI (SR-BI)- and ATP-binding cassette transporter 1 (ABCA1)-mediated efflux were examined by overexpressing either endothelial lipase (EL) or phosphatidylserine phospholipase (PS-PLA1) in human apoA-I transgenic mice. Overexpression of EL led to large reductions in the serum PL/apoA-I ratio (-60%), total cholesterol (TC, -89%), and HDL-C (-91%). Relative to the serum before overexpression of EL, the efflux potential of the serum via SR-BI decreased by 90% while ABCA1-mediated efflux increased by 63%. In contrast to overexpression of EL, overexpression of PS-PLA1 led to increases in the PL/apoA-I ratio (88%), TC (78%), and HDL-C (57%), and HDL size. The efflux potential of the serum increased by 60% via SR-BI and decreased by 57% by ABCA1. There were significant positive correlations between SR-BI-mediated efflux and a number of serum parameters including PL/apoA-I ratio, PL, TC, FC, and HDL-C. In striking contrast, the same correlations were seen with ABCA1-mediated efflux, but the relationships were inverse. In summary, in vivo modulation of HDL PL content affects ABCA1- and SR-BI-mediated efflux in a reciprocal fashion. These findings indicate that the type of lipase acting on HDL in vivo will determine which FC efflux pathway the HDL serves. Additionally, the extent of lipolysis will determine the efficiency of FC removal via this pathway.


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