Cytoplasmic expression and extracellular deposition of an antiangiogenic factor, pigment epithelium-derived factor, in human atherosclerotic plaques

Cytoplasmic expression and extracellular deposition of an antiangiogenic factor, pigment epithelium-derived factor, in human atherosclerotic plaques
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DOI:
10.1161/01.atv.0000175759.78338.1e
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发表时间:
2005-09-01
影响因子:
8.7
通讯作者:
Sueishi, K
Sueishi, K
中科院分区:
医学1区
文献类型:
--
作者:
Baba, H;Yonemitsu, Y;Sueishi, K

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目的 - 评估与血管生成相关的神经营养/抗血管生成因子、色素上皮衍生因子 (PEDF) 的表达和分布,血管生成可能是人类动脉粥样硬化斑块动脉粥样硬化形成过程中的关键事件。 方法和结果 - 使用 20 份新鲜主动脉样本进行逆转录聚合酶链反应 (RT-PCR)、蛋白质印迹和免疫印迹分析。 免疫组织化学(IHC)。此外,还使用了来自 40 个尸检病例的 80 个储存的冠状动脉石蜡块。 IHC 显示,在所测试的主动脉和冠状动脉中,PEDF 的染色模式不同,即分别观察到“细胞质染色”或“细胞外沉积”。在细胞质染色区域,大部分泡沫巨噬细胞和部分平滑肌细胞均表达双PEDF,PEDF阳性细胞频率与冠状动脉细胞丰富区微血管频率呈正相关(P < 0.0001)。相反,PEDF 的细胞外沉积出现在无细胞区域,并且与微血管数量呈负相关 (P = 0.0003)。结论 - 这些结果表明,当 PEDF 沉积到细胞外基质上时,它可能起到抗血管生成因子的作用。因此,PEDF可能在动脉粥样硬化形成过程中决定血管生成/抗血管生成的平衡中发挥重要作用。
Objective - To assess the expression and distribution of a neurotrophic/ antiangiogenic factor, pigment epithelium-derived factor ( PEDF), related to angiogenesis that is a possibly key event during atherogenesis in human atherosclerotic plaques.Methods and Results - Twenty fresh aortic samples were used for reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry (IHC). In addition, 80 stocked paraffin blocks of coronary arteries from 40 autopsy cases were also used. IHC revealed divergent staining patterns for PEDF in both the aortas and the coronary arteries tested, ie, "cytoplasmic staining" or "extracellular deposition," were observed, respectively. In the areas showing cytoplasmic staining, double PEDF was expressed in a majority of the foamy macrophages and in some smooth muscle cells, and the PEDF-positive cell frequency was positively correlated with that of microvessels in a cell-rich area in the coronary arteries ( P < 0.0001). Inversely, extracellular deposition of PEDF was seen in acellular areas and was negatively correlated with the number of microvessels ( P = 0.0003).Conclusions - These results suggest that PEDF may function as an antiangiogenic factor when it is deposited onto the extracellular matrix. Thus, PEDF may play a significant role in determining the balance of angiogenesis/ antiangiogenesis during atherogenesis.