Submitted on February 1, 2005
Revised on April 12, 2005
Accepted on May 2, 2005
Biogenesis and speciation of nascent apoA-I-containing particles in various cell lines
Larbi Krimbou, Houssein Hajj Hassan, Sacha Blain, Shirya Rashid, Maxime Denis, Michel Marcil, and Jacques Genest
Department of Cardiology, McGill University Health Center, Montreal, QC H3A 1A1
Corresponding Author: 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 apoA-I with either fibroblasts, CaCo-2 or CHO-overexpressing ABCA1 cells generates only 
LpA-I with diameters of 8 to 20 nm, whereas HUVEC 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 pre
1LpA-I. Furthermore, glyburide inhibits almost completely the formation of LpA-I but not pre1LpA-I. Similarly, endogenously secreted HepG2 apoA-I was found associated with both pre1LpA-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 rHDL was reacted with LCAT. Although both particles had similar Vmax (8.4 vs. 8.2 nmol CE/h/µg LCAT, respectively), the Km value was increased 2-fold for LpA-I compared to rHDL (1.2 vs. 0.7 µM apoA-I). These results demonstrate that: 1) ABCA1 is required for the formation of LpA-I but not pre1LpA-I; and 2) nascent 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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
