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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2022.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Wild-Type ApoA-I and the Milano Variant Have Similar Abilities to Stimulate Cellular Lipid Mobilization and Efflux

Ginny L. Weibel; Eric T. Alexander; Michelle R. Joshi; Daniel J. Rader; Sissel Lund-Katz; Michael C. Phillips; George H. Rothblat

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.

Correspondence to Ginny L. Weibel, Division of Gasteroenterology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104-4399. 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-I_Milano, reconstituted high-density lipoprotein (rHDL) particles containing these proteins and serum isolated from mice expressing human apoA-I or apoA-I_Milano.

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-I_wt). Additionally, intracellular cholesteryl ester hydrolysis in macrophage foam cells was not different in the presence of either apoA-I_Milano or apoA-I_wt.

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.

The present study is a comparative investigation of cellular lipid mobilization to human apoA-I and apoA-I_Milano. Efflux was measured in cell systems designed to assess the contributions ABCA1 and SR-BI. Acceptors containing the Milano variant of apoA-I showed no functional increase in lipid efflux when compared with wild-type apoA-I.

Key Words: apolipoprotein • A-I • HDL • cholesterol efflux • apoA-I_Milano

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