Tie endothelial cell-specific receptor tyrosine kinase is upregulated in the vasculature of arteriovenous malformations
Tie endothelial cell-specific receptor tyrosine kinase is upregulated in the vasculature of arteriovenous malformations
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DOI：
10.1097/00005072-199611000-00003
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发表时间：
1996-11-01
影响因子：
3.2
通讯作者：
Haltia, M
中科院分区：
文献类型：
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作者：
Hatva, E;Jaaskelainen, J;Haltia, M
动静脉畸形（AVM）是由异常血管系统组成的先天性病变，无毛细血管成分。并且由于其自发出血的倾向而具有临床意义。调节这些病变的发生和进展的机制尚不清楚。为了研究AVM血管生成的规律，我们采用原位杂交和免疫组织化学方法，检测了血管内皮细胞有丝分裂原血管内皮生长因子（VEGF）和一种新的内皮细胞特异性受体酪氨酸激酶（Tie）在AVM及其周围脑组织中的表达。我们先前已经显示Tie的上调伴随伤口愈合和肿瘤进展。在这项研究中，我们证明了Tie mRNA和蛋白在AVM和周围脑血管中的水平显著升高。VEGF mRNA在AVM周围脑实质细胞中表达上调，VEGF蛋白在该组织和AVM内皮细胞中也有表达。相比之下，正常大脑表达很少或没有Tie或VEGF。AVM中VEGF和Tie的显著上调可能表明一些正在进行的血管生成，可能有助于AVM的缓慢生长和维持，并且可能在这些病变的治疗靶向中具有潜在用途。
Arteriovenous malformations (AVMs) are congenital lesions composed of abnormal vasculature, with no capillary component. and are clinically significant due to their tendency to spontaneously hemorrhage. The mechanisms regulating the genesis and progression of these lesions are unknown. In order to study the rule of angiogenesis in AVMs, we have analyzed the expression of the endothelial cell mitogen vascular endothelial growth factor (VEGF) and a novel endothelial cell-specific receptor tyrosine kinase, Tie, by in situ hybridization and immunohistochemistry in these malformations and surrounding brain tissue. We have previously shown upregulation of Tie accompanying wound healing and tumor progression. In this study, we demonstrate significantly elevated levels of Tie mRNA and protein in AVM and surrounding brain vasculature. Upregulation of VEGF mRNA was observed in the cells of brain parenchyma adjacent to the AVM, and VEGF protein was detected in this tissue as well as in AVM endothelia. Normal brain, in comparison, expressed little or no Tie or VEGF. The significant upregulation of VEGF and Tie in AVMs may indicate some ongoing angiogenesis, possibly contributing to the slow growth and maintenance of the AVM, and could be of potential use in the therapeutic targeting of these lesions.