| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Research Abstract |
Endothelial cells and pericytes play critical role in angiogenesis, which is controlled, in part, by the angiopoietin (Ang)/Tie-2 system and vascular endothelial growth factor (VEGF). Endothelial cell and pericyte interdigitations(EPI), consisting of cytoplasmic projections of pericytes and corresponding endothelial indentations, are frequently present at angiogenic sites. After subcutaneous implantation of a thermoreversible gelation polymer disc in rats, the capillary density was low on day 5, increased to a peak on day 7, and then decreased on days 10-20. A small number of EPI were observed on day 5, then increased sharply to a peak on day 10, but had decreased on day 20. Light and electron microscopy immunohistochemical and RNA in situ hybridization analyses revealed that Tie-2 localized at endothelial cells, and Ang-2 localized at endothelial cells and pericytes, while Ang-1 and VEGF localized at pericytes, and Ang-1 was most intensely observed at EPI of pericytes. Conventional, quantitative RT-PCR and Western blot analyses revealed that the level of Ang-1 was low on days 5-7, and then increased on days 10-20, while the level of VEGF was high on days 5-10, but had decreased on day 20. The expression of Ang-2 and Tie-2 was unchanged on days 5-20. The present study showed that the angiogenic phase might be initiated by Ang-2 and VEGF, while the microvessel maturation phase might to be initiated by Ang-1 and VEGF. Moreover, EPI might act as a pathway for the Ang-1/Tie-2 system with VEGF promoting pericyte recruitment for microvascular integrity.
|
