Hatva E, Jääskeläinen J, Hirvonen H, Alitalo K, Haltia M
Neurobiology Laboratory, Haartman Institute, University of Helsinki, Haartmaninkatu, Finland.
J Neuropathol Exp Neurol. 1996 Nov;55(11):1124-33. doi: 10.1097/00005072-199611000-00003.
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 role 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.
动静脉畸形（AVM）是由异常血管组成的先天性病变，没有毛细血管成分，由于其有自发出血的倾向，因此具有临床意义。调节这些病变发生和发展的机制尚不清楚。为了研究血管生成在AVM中的作用，我们通过原位杂交和免疫组织化学分析了内皮细胞促有丝分裂原血管内皮生长因子（VEGF）和一种新型内皮细胞特异性受体酪氨酸激酶Tie在这些畸形及其周围脑组织中的表达。我们之前已经证明Tie在伤口愈合和肿瘤进展过程中上调。在本研究中，我们证明AVM及其周围脑血管中Tie mRNA和蛋白水平显著升高。在AVM相邻的脑实质细胞中观察到VEGF mRNA上调，并且在该组织以及AVM内皮中检测到VEGF蛋白。相比之下，正常脑组织几乎不表达或不表达Tie或VEGF。AVM中VEGF和Tie的显著上调可能表明存在一些正在进行的血管生成，这可能有助于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。
