Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques - Colocalization of biglycan with apolipoproteins
Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques - Colocalization of biglycan with apolipoproteins
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DOI：
10.1161/01.cir.98.6.519
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发表时间：
1998-08-11
期刊：
影响因子：
37.8
通讯作者：
Chait, A
中科院分区：
文献类型：
--
作者：
O'Brien, KD;Olin, KL;Chait, A
背景-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，并且体外研究表明蛋白聚糖在介导斑块载脂蛋白（apo）保留中发挥作用，因此进行免疫组织化学来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。对 68 个人类冠状动脉节段进行了 apoE 比较；还对另外 20 个片段对 apoA-I 和 apoB 进行了评估。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 沉积物则少得多。相比之下，几乎所有动脉粥样硬化部分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存在高度共定位。 ApoA-I（HDL 的主要载脂蛋白）和 apoB 也在有 apoE 和双糖链蛋白聚糖沉积的区域中检测到。在由于坏死或密集巨噬细胞聚集而缺乏完整细胞外基质的区域中发现了双糖链蛋白与载脂蛋白定位的异常。体外研究表明，双糖链蛋白聚糖可结合含有apoE但不结合不含apoE的HDL，并且双糖链蛋白聚糖还结合LDL。结论-这些结果表明双糖链蛋白聚糖可能结合动脉粥样硬化内膜中的apoE和apoB。他们还提出了一种可能性，apoE 可能充当“桥接”分子，将含有 apoA-I 的 HDL 捕获在动脉粥样硬化内膜中。总而言之，这些发现与双糖链蛋白聚糖可能通过将脂蛋白捕获在动脉壁中而促进动脉粥样硬化的发病机制的假设相一致。
Background-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.Methods and Results-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.Conclusions-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.