on July 5, 2007
Published online before print July 5, 2007, doi: 10.1161/ATVBAHA.107.148403
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Submitted on May 21, 2007
Accepted on June 15, 2007
Wild-Type ApoA-I and the Milano Variant Have Similar Abilities to Stimulate Cellular Lipid Mobilization and Efflux
Ginny L. Weibel *;
From the Division of Gasteroenterology and Nutrition (G.L.W., E.T.A., M.R.J., S.L-K., M.C.P., G.H.R.), The Children’s Hospital of Philadelphia, and the Department of Medicine (D.J.R.), University of Pennsylvania School of Medicine, Philadelphia, Pa.
* To whom correspondence should be addressed. E-mail: weibel{at}email.chop.edu.
Objective--The present study is a comparative investigation of cellular lipid mobilization and efflux to lipid-free human apoA-I and apoA-IMilano, reconstituted high-density lipoprotein (rHDL) particles containing these proteins and serum isolated from mice expressing human apoA-I or apoA-IMilano.
Methods and Results--Cholesterol and phospholipid efflux to these acceptors was measured in cell systems designed to assess the contributions of ATP-binding cassette A1 (ABCA1), scavenger receptor type BI (SRBI), and cellular lipid content to cholesterol and phospholipid efflux. Acceptors containing the Milano variant of apoA-I showed no functional increase in lipid efflux in all assays when compared with wild-type apoA-I. In fact, in some systems, acceptors containing the Milano variant of apoA-I promoted significantly less efflux than the acceptors containing wild-type apoA-I (apoA-Iwt). Additionally, intracellular cholesteryl ester hydrolysis in macrophage foam cells was not different in the presence of either apoA-IMilano or apoA-Iwt.
Conclusion--Collectively these studies suggest that if the Milano variant of apoA-I offers greater atheroprotection than wild-type apoA-I, it is not attributable to greater cellular lipid mobilization.
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