Morphologic, Phenotypic and Functional Characteristics of Endothelial Cells Derived from Human Hepatic Cavernous Hemangioma

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). Methods and Results: 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 αvβ3 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. Conclusion: These results suggested that endothelial cells (ECs) derived from human cavernous hemangiomas differ from normal ECs in morphology, phenotype and function.