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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1301.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Well-Defined Regions of Apolipoprotein B-100 Undergo Conformational Change During Its Intravascular Metabolism

Xingyu Wang; Richard Pease; Jesse Bertinato; Ross W. Milne

From the Lipoprotein and Atherosclerosis Research Group and the Departments of Pathology and Biochemistry, Microbiology, and Immunology, University of Ottawa Heart Institute (X.W., J.B., R.W.M.), Ottawa, Ontario, Canada; the Sino-German Laboratory, Cardiovascular Institute (X.W.), Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China; and the Department of Biochemistry and Molecular Biology, University College London (R.P.), London, UK.

Correspondence to Ross Milne, PhD, Room H450, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7. E-mail rmilne{at}ottawaheart.ca

Abstract—Apolipoprotein B (apoB)-100–containing lipoproteins are secreted from the liver as large triglyceride-rich very low density lipoproteins (VLDLs) into the circulation, where they are transformed, through the action of lipases and plasma lipid transfer proteins, into smaller, less buoyant, cholesteryl ester–rich low density lipoproteins (LDLs). As a consequence of this intravascular metabolism, apoB-containing lipoproteins are heterogeneous in size, in hydrated density, in surface charge, and in lipid and apolipoprotein composition. To identify specific regions of apoB that may undergo conformational changes during the intravascular transformation of VLDLs into LDLs, we have used a panel of 29 well-characterized anti-apoB monoclonal antibodies to determine whether individual apoB epitopes are differentially expressed in VLDL, intermediate density lipoprotein (IDL), and LDL subfractions isolated from 6 normolipidemic subjects. When analyzed in a solid-phase radioimmunoassay, the expression of most epitopes was remarkably similar in VLDLs, IDLs, and LDLs. Two epitopes that are close to the apoB LDL receptor–binding site show an increased expression in large (1.019 to 1.028 g/mL), medium (1.028 to 1.041 g/mL), and small (1.041 to 1.063 g/mL) LDLs compared with VLDLs and IDLs, and 2 epitopes situated between apoB residues 4342 and 4536 are significantly more immunoreactive in small and medium-sized LDLs compared with VLDLs, IDLs, and large LDLs. Therefore, as VLDL is converted to LDL, conformational changes identified by monoclonal antibodies occur at precise points in the metabolic cascade and are limited to well-defined regions of apoB structure. These conformational changes may correspond to alterations in apoB functional activities.

Key Words: apolipoprotein B • intravascular metabolism • lipoproteins

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