Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Cell & Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Int J Mol Sci. 2022 Aug 14;23(16):9109. doi: 10.3390/ijms23169109.
Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.
动静脉畸形(AVM)的特征是动脉和静脉之间没有毛细血管的高血流血管连接。这种疾病表现为近端组织中血管生成增加和病理缺氧环境。在这里,我们分析了缺氧对 AVM 和正常组织内皮细胞(EC)血管生成的影响。使用 CD31 通过免疫细胞化学评估来自人正常和 AVM 组织的 EC。在 Matrigel 中在体外缺氧条件下测试 EC 的管状形成。使用实时 PCR 测量血管生成相关基因的相对表达。在常氧条件下,AVM EC 中的 CD31 明显高于正常 EC(79.23±0.65%)(74.15±0.70%)。在 AVM EC(63.85±1.84%)和正常 EC(60.52±0.51%)中也观察到了类似的结果。在常氧和缺氧条件下的管状形成试验中,AVM EC 的连接计数和总血管长度明显大于正常 EC。在常氧和缺氧条件下,AVM EC 中的血管生成相关基因表达均明显高于正常 EC。在缺氧条件下,AVM EC 中的表达明显低于正常 EC。因此,与正常 EC 相比,AVM EC 的血管生成作用增加。这些结果为 AVM 治疗策略提供了基础知识。