ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36.
The class B scavenger receptors SR-BI and CD36 exhibit a broad ligand binding specificity. SR-BI is well characterized as a HDL receptor that mediates selective cholesteryl ester uptake from HDL. CD36, a receptor for oxidized LDL, also binds HDL and mediates selective cholesteryl ester uptake, although much less efficiently than SR-BI. Apolipoprotein A-II (apoA-II), the second most abundant HDL protein, is considered to be proatherogenic, but the underlying mechanisms are unclear. We previously showed that apoA-II modulates SR-BI-dependent binding and selective uptake of cholesteryl ester from reconstituted HDL. To investigate the effect of apoA-II in naturally occurring HDL on these processes, we compared HDL without apoA-II (from apoA-II null mice) with HDLs containing differing amounts of apoA-II (from C57BL/6 mice and transgenic mice expressing a mouse apoA-II transgene). The level of apoA-II in HDL was inversely correlated with HDL binding and selective cholesteryl ester uptake by both scavenger receptors, particularly CD36. Interestingly, for HDL lacking apoA-II, the efficiency with which CD36 mediated selective uptake reached a level similar to that of SR-BI. These results demonstrate that apoA-II exerts a marked effect on HDL binding and selective lipid uptake by the class B scavenger receptors and establishes a potentially important relationship between apoA-II and CD36.
de Beer
Maria C
MC
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Castellani
Lawrence W
LW
Cai
Lei
L
Stromberg
Arnold J
AJ
de Beer
Frederick C
FC
van der Westhuyzen
Deneys R
DR
D000818:Animals; D016633:Apolipoprotein A-II / Q000235:genetics / Q000502:physiology*; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D016633:Apolipoprotein A-II; D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; C099252:oxidized low density lipoprotein