The roles of vascular endothelial growth factor and angiopoietin-2 in the regression of pregnancy pyogenic granuloma.
OBJECTIVE
The molecular mechanism for the regression of pregnancy pyogenic granuloma after parturition remains unclear. It has been proposed that, in the absence of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) causes blood vessels to regress. Therefore, we investigated the roles of Ang-2 and VEGF in the regression of pregnancy pyogenic granuloma.


METHODS
The effects of tumor necrosis factor-alpha (TNF-alpha) on the transcription of Ang-2 were tested in endothelial cells by reverse transcriptase-polymerase chain reaction. A total of 15 specimens, including granulomas taken from five gravidas during pregnancy, five after parturition, and five from normal gingiva were compared by immunoblot assays for their relative expressions of Ang-1, Ang-2, Tie-2, VEGF, and beta-actin. Double staining, immunohistochemistry for Ang-2, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling for apoptotic cells, were used to evaluate their regression. Finally, a fibrin gel culture system was used to investigate whether the withdrawal of VEGF and addition of Ang-2 could cause newly grown microvessels to regress.


RESULTS
TNF-alpha upregulated the expression of Ang-2 in all endothelial cell types tested. The protein levels of Ang-2 and Tie-2 were highest in the granulomas in pregnancy, followed by those after parturition and normal gingiva, while Ang-1 and beta-actin exhibited no significant differences. The amount of VEGF was high in the granulomas in pregnancy and almost undetectable after parturition. Double staining on granulomas after parturition revealed more apoptotic cells and less Ang-2 than did those in pregnancy. In the fibrin gel assay, VEGF alone or in combination with Ang-2 could protect microvessels from apoptosis, while Ang-2 alone had no effect.


CONCLUSIONS
Our findings suggest that a lack of VEGF is associated with apoptosis of endothelial cells and regression of granuloma. The roles of Ang-2 require additional study.
Yuan
K
K
Periodontics Division, Department of Dentistry, National Cheng Kung University Hospital, Tainan, Taiwan.
Lin
M T
MT
D000199:Actins / Q000032:analysis; D000328:Adult; D042683:Angiopoietin-1 / Q000032:analysis; D042702:Angiopoietin-2 / Q000032:analysis / Q000502:physiology*; D017209:Apoptosis; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005882:Gingival Diseases / Q000378:metabolism / Q000503:physiopathology*; D017789:Granuloma, Pyogenic / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008833:Microcirculation / Q000187:drug effects; D036801:Parturition; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000503:physiopathology*; D042787:Receptor, TIE-2 / Q000032:analysis; D012075:Remission, Spontaneous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000502:physiology*
D000199:Actins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2