O'Brien K D, Olin K L, Alpers C E, Chiu W, Ferguson M, Hudkins K, Wight T N, Chait A
Department of Medicine, University of Washington, Seattle 98195, USA.
Circulation. 1998 Aug 11;98(6):519-27. doi: 10.1161/01.cir.98.6.519.
Because the content of specific proteoglycans and apolipoproteins is increased in atherosclerotic plaques and in vitro studies have suggested a role for proteoglycans in mediating plaque apolipoprotein (apo) retention, immunohistochemistry was performed to systematically examine the relative locations of proteoglycans and apolipoproteins in human atherosclerosis.
The spatial relationships of versican, biglycan, and apoE were compared on 68 human coronary artery segments; apoA-I and apoB also were evaluated on an additional 20 segments. Nonatherosclerotic intima contained extensive deposits of versican, whereas deposits of apoE, apoB, and apoA-I were much less prevalent. In contrast, nearly all atherosclerotic segments contained substantial deposits of biglycan, apoE, apoA-I, and apoB. There was a high degree of colocalization of apoE and biglycan deposits. ApoA-I, the major apolipoprotein of HDL, and apoB also were detected in regions with apoE and biglycan deposition. Exceptions to the localization of biglycan with apolipoproteins were found in regions that lacked intact extracellular matrix because of necrosis or dense macrophage accumulation. In vitro studies demonstrated that biglycan binds apoE-containing but not apoE-free HDL and that biglycan also binds LDL.
These results suggest that biglycan may bind apoE and apoB in atherosclerotic intima. They also raise the possibility that apoE may act as a "bridging" molecule that traps apoA-I-containing HDL in atherosclerotic intima. Taken together, these findings are consistent with the hypothesis that biglycan may contribute to the pathogenesis of atherosclerosis by trapping lipoproteins in the artery wall.
由于动脉粥样硬化斑块中特定蛋白聚糖和载脂蛋白的含量增加，且体外研究表明蛋白聚糖在介导斑块载脂蛋白（apo）滞留中发挥作用，因此进行了免疫组织化学研究，以系统地检查蛋白聚糖和载脂蛋白在人类动脉粥样硬化中的相对位置。
在68个人类冠状动脉节段上比较了多功能蛋白聚糖、双糖链蛋白聚糖和载脂蛋白E（apoE）的空间关系；另外20个节段还评估了载脂蛋白A-I（apoA-I）和载脂蛋白B（apoB）。非动脉粥样硬化内膜含有大量多功能蛋白聚糖沉积物，而apoE、apoB和apoA-I的沉积物则较少见。相比之下，几乎所有动脉粥样硬化节段都含有大量双糖链蛋白聚糖、apoE、apoA-I和apoB沉积物。apoE和双糖链蛋白聚糖沉积物高度共定位。在apoE和双糖链蛋白聚糖沉积区域也检测到了HDL的主要载脂蛋白apoA-I和apoB。在因坏死或密集巨噬细胞聚集而缺乏完整细胞外基质的区域发现了双糖链蛋白聚糖与载脂蛋白定位的例外情况。体外研究表明，双糖链蛋白聚糖结合含apoE的HDL而非不含apoE的HDL，并且双糖链蛋白聚糖也结合低密度脂蛋白（LDL）。
这些结果表明，双糖链蛋白聚糖可能在动脉粥样硬化内膜中结合apoE和apoB；它们还提出了apoE可能作为“桥接”分子将含apoA-I的HDL捕获在动脉粥样硬化内膜中的可能性。综上所述，这些发现与双糖链蛋白聚糖可能通过在动脉壁中捕获脂蛋白而促进动脉粥样硬化发病机制的假说一致。
