Chiu D S, Oram J F, LeBoeuf R C, Alpers C E, O'Brien K D
Division of Cardiology, University of Washington 98195-6422, USA.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2350-8. doi: 10.1161/01.atv.17.11.2350.
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.
动脉内膜细胞内胆固醇酯的蓄积是动脉粥样硬化的一个标志。少数蛋白质已在体外实验中被证明会因细胞胆固醇负荷而表达上调，包括载脂蛋白E（apoE）和最近克隆的高密度脂蛋白结合蛋白（HBP），但只有apoE在动脉粥样硬化中胆固醇负荷的细胞中被证明表达上调。为了确定HBP（也称为vigilin）是否可能在人类动脉粥样硬化中表达，对18例患者的冠状动脉进行了免疫组织化学和原位杂交检测。在所有内皮细胞上均检测到HBP/vigilin。在动脉粥样硬化斑块中的一部分巨噬细胞上也检测到了HBP/vigilin mRNA和蛋白质，偶尔在平滑肌细胞（SMC）上也有检测到，但在未患病的冠状动脉内膜的这些细胞类型上未检测到。大多数表达HBP/vigilin的巨噬细胞是泡沫细胞，但在非泡沫细胞巨噬细胞中也很少检测到HBP/vigilin的表达。在100%的动脉粥样硬化象限中存在泡沫细胞巨噬细胞HBP/vigilin表达，在6%的动脉粥样硬化象限中存在非泡沫细胞巨噬细胞HBP/vigilin表达。表达HBP/vigilin的人类斑块细胞也表达apoE。然而，在apoE缺陷小鼠的心肌细胞泡沫细胞中检测到了HBP/vigilin，这表明HBP/vigilin的表达可以独立于apoE发生。这些结果表明，在体内HBP/vigilin的表达因细胞内胆固醇负荷而上调，但动脉粥样硬化斑块中存在的其他因素也可能上调HBP/vigilin。尽管HBP/vigilin的确切功能尚不清楚，但其在斑块巨噬细胞中的表达表明该分子在动脉粥样硬化形成中起作用。
