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Journal of Lipid Research, Vol. 46, 1668-1677, August 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
Cardiovascular Genetics Laboratory, Cardiology Division, McGill University Health Centre/Royal Victoria Hospital, Montréal, Québec H3A 1A1, Canada
Published, JLR Papers in Press, May 16, 2005. DOI 10.1194/jlr.M500038-JLR200
1 To whom correspondence should be addressed. e-mail: jacques.genest{at}muhc.mcgill.ca
It is generally thought that the large heterogeneity of human HDL confers antiatherogenic properties; however, the mechanisms governing HDL biogenesis and speciation are complex and poorly understood. Here, we show that incubation of exogenous apolipoprotein A-I (apoA-I) with fibroblasts, CaCo-2, or CHO-overexpressing ABCA1 cells generates only 
-nascent apolipoprotein A-I-containing particles (-LpA-I) with diameters of 8–20 nm, whereas human umbilical vein endothelial cells and ABCA1 mutant (Q597R) cells were unable to form such particles. Interestingly, incubation of exogenous apoA-I with either HepG2 or macrophages generates both -LpA-I and preß1-LpA-I. Furthermore, glyburide inhibits almost completely the formation of -LpA-I but not preß1-LpA-I. Similarly, endogenously secreted HepG2 apoA-I was found to be associated with both preß1-LpA-I and -LpA-I; by contrast, CaCo-2 cells secreted only -LpA-I. To determine whether -LpA-I generated by fibroblasts is a good substrate for LCAT, isolated -LpA-I as well as reconstituted HDL [r(HDL)] was reacted with LCAT. Although both particles had similar Vmax (8.4 vs. 8.2 nmol cholesteryl ester/h/µg LCAT, respectively), the Km value was increased 2-fold for -LpA-I compared with r(HDL) (1.2 vs. 0.7 µM apoA-I).
These results demonstrate that 1) ABCA1 is required for the formation of -LpA-I but not preß1-LpA-I; and 2) -LpA-I interacts efficiently with LCAT. Thus, our study provides direct evidence for a new link between specific cell lines and the speciation of nascent HDL that occurs by both ABCA1-dependent and -independent pathways.
Abbreviations: apoA-I, apolipoprotein A-I; CE, cholesteryl ester; HUVEC, human umbilical vein endothelial cells; LpA-I, nascent apolipoprotein A-I-containing particle; MWCO, molecular weight cut off; RCT, reverse cholesterol transport; r(HDL), reconstituted high density lipoprotein; TD, Tangier disease; 2D-PAGGE, two-dimensional polyacrylamide nondenaturing gradient gel electrophoresis; 22OH/9CRA, 22(R)-hydroxycholesterol and 9-cis-retinoic acid
Supplementary key words ATP binding cassette transporter A1 • high density lipoprotein • -nascent apolipoprotein A-I-containing particle • pre-ß1-nascent apolipoprotein A-I-containing particle
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