Evidence that endothelial lipase remodels high density lipoproteins without mediating the dissociation of apolipoprotein A-I.
Endothelial lipase (EL) is a triglyceride lipase gene family member that has high phospholipase and low triglyceride lipase activity. The aim of this study was to determine whether the phospholipase activity of EL is sufficient to remodel HDLs into small particles and mediate the dissociation of apolipoprotein A-I (apoA-I). Spherical, reconstituted HDLs (rHDLs) containing apoA-I only [(A-I)rHDLs], apoA-II only [(A-II)rHDLs], or both apoA-I and apoA-II [(A-I/A-II) rHDLs] were prepared. The rHDLs, which contained only cholesteryl esters in their core and POPC on the surface, were incubated with EL. As the rHDLs did not contain triacylglycerol, only the POPC was hydrolyzed. Hydrolysis was greater in the (A-I/A-II)rHDLs than in the (A-I)rHDLs. The (A-II)rHDL phospholipids were not hydrolyzed by EL. EL remodeled the (A-I)rHDLs and (A-I/A-II)rHDLs, but not the (A-II)rHDLs, into smaller particles. The reduction in particle size was related to the amount of phospholipid hydrolysis, with the diameter of the (A-I/A-II)rHDLs decreasing more than that of the (A-I)rHDLs. These changes did not affect the conformation of apoA-I, and neither apoA-I nor apoA-II dissociated from the rHDLs. Comparable results were obtained when human plasma HDLs were incubated with EL. These results establish that the phospholipase activity of EL remodels plasma HDLs and rHDLs into smaller particles without mediating the dissociation of apolipoproteins.
Jahangiri
A
A
Lipid Research Group, Heart Research Institute, Camperdown, Sydney, New South Wales 2050, Australia. a.jahangiri@hri.org.au
Rader
D J
DJ
Marchadier
D
D
Curtiss
L K
LK
Bonnet
D J
DJ
Rye
K-A
KA
D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood*; D011487:Protein Conformation; D020349:Surface Plasmon Resonance
D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; C410382:LIPG protein, human; D008049:Lipase