High-density lipoprotein-binding protein (HBP)/vigilin is expressed in human atherosclerotic lesions and colocalizes with apolipoprotein E.
Accumulation of cholesteryl esters within cells of the arterial intima is a hallmark of atherosclerosis. A small number of proteins have been shown in vitro to be upregulated by cellular cholesterol loading, including apolipoprotein E (apoE) and the recently cloned HDL-binding protein (HBP), but only apoE has been shown to be upregulated in cholesterol-loaded cells in atherosclerosis. To determine whether HBP (also called vigilin) might be expressed in human atherosclerosis, immunohistochemistry and in situ hybridization were performed on coronary arteries of 18 patients. HBP/vigilin was detected on all endothelial cells. HBP/vigilin mRNA and protein also were detected on a subset of macrophages and occasionally on smooth muscle cells (SMC) in atherosclerotic plaques but were not detected on these cell types in nondiseased coronary intima. The majority of HBP/vigilin-expressing macrophages were foam cells, but HBP/vigilin expression also was detected rarely in nonfoam cell macrophages. Foam cell macrophage HBP/vigilin expression was present in 100% of atherosclerotic quadrants, and nonfoam cell macrophage HBP/vigilin expression was present in 6% of atherosclerotic quadrants. HBP/vigilin-expressing human plaque cells also expressed apoE. However, HBP/vigilin was detected in cardiac myocyte foam cells of an apoE-deficient mouse, demonstrating that HBP/vigilin expression can occur independently of apoE. These results suggest that in vivo HBP/vigilin expression is upregulated by intracellular cholesterol loading but also that other factors present in atherosclerotic plaques may upregulate HBP/vigilin. Although the exact function of HBP/vigilin is unknown, its expression in plaque macrophages suggests a role for this molecule in atherogenesis.
Chiu
D S
DS
Division of Cardiology, University of Washington 98195-6422, USA.
Oram
J F
JF
LeBoeuf
R C
RC
Alpers
C E
CE
O'Brien
K D
KD
D000595:Amino Acid Sequence; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D011817:Rabbits
D001057:Apolipoproteins E; D002352:Carrier Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C075197:high density lipoprotein binding protein; D002784:Cholesterol