Critical overexpression of thrombospondin I in chronic leg ischaemia
Critical overexpression of thrombospondin I in chronic leg ischaemia
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DOI：
10.1002/path.1833
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发表时间：
2005-11-01
影响因子：
7.3
通讯作者：
Gasc, JM
中科院分区：
文献类型：
--
作者：
Favier, J;Germain, S;Gasc, JM
本研究的目的是确定控制人类缺血腿部组织中血管生成和血管抑制因子平衡的基因表达。采用原位杂交技术筛选 13 例腿部严重缺血患者截肢组织中血管生成相关基因的表达情况。作者测试了缺氧诱导转录因子 1 α 和 2 α、血管内皮生长因子及其受体 VEGFR-1 和 -2、血管生成素受体 Tie2 和抗血管生成分子血小板反应蛋白 1 的 mRNA。将这些基因在近端健康肌肉中的表达水平与远端缺血肌肉中的表达水平进行了比较。令人惊讶的是，在所有研究的患者腿部缺血部位中，只有血小板反应蛋白 1 过度表达。通过实时 RT-PCR 检测血小板反应蛋白 I mRNA，该基因过表达 20 倍。通过蛋白质印迹证实了其编码蛋白的存在。这种抗血管生成分子的过量产生与受影响肌肉中毛细血管密度的降低有关。因此，血小板反应蛋白 1 是慢性缺血的标志物，可能影响缺血组织中的血管生成。版权所有 (c) 2005 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
The aim of this study was to identify gene expression governing the balance of angiogenic and angiostatic factors in human ischaemic leg tissues. In situ hybridization was used to screen for the expression of angiogenesis-related genes in tissues from 13 amputated limbs from patients suffering from critical leg ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors 1 alpha and 2 alpha, vascular endothelial growth factor, and its receptors VEGFR-1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule thrombospondin 1. The expression levels of the genes in proximal, healthy muscles were compared with those in the distal, ischaemic counterparts. Surprisingly, only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all patients studied. Thrombospondin I mRNA was assayed by real-time RT-PCR and the gene was overexpressed 20-fold. The presence of its encoded protein was confirmed by western blotting. The overproduction of this anti-angiogenic molecule was associated with a decrease in capillary density in the affected muscles. Thrombospondin 1 is thus a marker of chronic ischaemia and may affect angiogenesis in ischaemic tissues. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.