Morphologic, phenotypic and functional characteristics of endothelial cells derived from human hepatic cavernous hemangioma.
OBJECTIVE
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).


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 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.


CONCLUSIONS
These results suggested that endothelial cells (ECs) derived from human cavernous hemangiomas differ from normal ECs in morphology, phenotype and function.
Zhang
Wen-Jian
WJ
Institute of Basic Medical Sciences, Peking Union Medical College, Peking, People's Republic of China.
Ye
Li-Ya
LY
Wu
Lian-Qiu
LQ
Xin
Yu-Ling
YL
Gu
Feng
F
Niu
Ji-Xiao
JX
Yang
Zhi-Hua
ZH
Zhu
Guang-Jin
GJ
Grau
Georges E
GE
Lou
Jin-Ning
JN
D042683:Angiopoietin-1 / Q000235:genetics; D042702:Angiopoietin-2 / Q000235:genetics; D001777:Blood Coagulation; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D042783:Endothelial Cells / Q000473:pathology* / Q000648:ultrastructure; D005342:Fibrinolysis; D005434:Flow Cytometry; D006392:Hemangioma, Cavernous / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D010973:Platelet Adhesiveness; D042787:Receptor, TIE-2 / Q000235:genetics; D014617:Vacuoles / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; D020782:Matrix Metalloproteinases