Zhang Wen-Jian, Ye Li-Ya, Wu Lian-Qiu, Xin Yu-Ling, Gu Feng, Niu Ji-Xiao, Yang Zhi-Hua, Zhu Guang-Jin, Grau Georges E, Lou Jin-Ning
Institute of Basic Medical Sciences, Peking Union Medical College, Peking, People's Republic of China.
J Vasc Res. 2006;43(6):522-32. doi: 10.1159/000095965. Epub 2006 Sep 28.
BACKGROUNDS/AIMS: The pathogenesis of cavernous hemangiomas is largely unknown, and it is speculated that abnormal vasculogenesis and angiogenesis may be involved. In this study, the characteristics of cavernous hemangioma endothelial cells (CHECs) derived from the human liver were analyzed in terms of morphology, phenotype and function and compared with human liver sinusoidal endothelial cells (LSECs).
By transmission electron microscopy, abnormally expanded endoplasmic reticulum (ER) and similarly arranged cytoplasmic vacuoles were only found in CHECs. Phenotypic analysis showed that the expression of alphavbeta3 was significantly increased in CHECs. mRNA expression of vascular endothelial growth factor A, and angiopoietins 1 and 2 was significantly increased in CHECs compared to LSECs. The functional analysis indicated that CHECs released more vascular endothelial growth factor A, produced significantly more pro-matrix metalloproteinase 2 (pro-MMP2) and activated MMP2, and exhibited higher procoagulant and fibrinolytic activities compared with LSECs. Confocal microscopy revealed that MMP2 was concentrated in some cytoplasmic granules of CHECs and was consistent with the distribution of expanded ER. CHECs exhibited more activated angiogenesis capacity and formed abnormal capillary-like structures in vitro.
These results suggested that endothelial cells (ECs) derived from human cavernous hemangiomas differ from normal ECs in morphology, phenotype and function.
背景/目的：海绵状血管瘤的发病机制尚不清楚，推测可能与异常的血管发生和血管生成有关。本研究从形态、表型和功能方面分析了来源于人肝脏的海绵状血管瘤内皮细胞（CHECs）的特征，并与人类肝窦内皮细胞（LSECs）进行了比较。
通过透射电子显微镜观察，仅在CHECs中发现内质网（ER）异常扩张和胞质空泡排列相似。表型分析表明，CHECs中αvβ3的表达显著增加。与LSECs相比，CHECs中血管内皮生长因子A、血管生成素1和2的mRNA表达显著增加。功能分析表明，与LSECs相比，CHECs释放更多的血管内皮生长因子A，产生显著更多的前基质金属蛋白酶2（pro-MMP2）并激活MMP2，且表现出更高的促凝血和纤溶活性。共聚焦显微镜显示，MMP2集中在CHECs的一些胞质颗粒中，并与扩张的ER分布一致。CHECs在体外表现出更强的血管生成激活能力，并形成异常的毛细血管样结构。
这些结果表明，来源于人类海绵状血管瘤的内皮细胞（ECs）在形态、表型和功能上与正常ECs不同。
