Temporal Changes of Angiopoietins and Tie2 Expression in Rat Lungs after Monocrotaline-Induced Pulmonary Hypertension

Angiogenic factors such as vascular endothelial growth factor (VEGF) are implicated in pulmonary hypertension (PH). However, the pathway of angiogenic factor-mediated pathologic angiogenesis in PH remains unclear. In this study, we evaluated the temporal expression of angiopoietin (Ang) 1, Ang2, and...

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Bibliographic Details
Published in:Comparative medicine 2009-08, Vol.59 (4), p.350-356
Main Authors: Cho, Yu Ji, Han, Jae Yoon, Lee, Sang Gab, Jeon, Byeong Tak, Choi, Wan Sung, Hwang, Young Sil, Roh, Gu Seob, Lee, Jong Deog
Format: Article
Language:English
Subjects:
angiogenic factors
Angiopoietin-1 - metabolism
Angiopoietin-2 - metabolism
animal disease models
animal proteins
Animals
arteries
Blotting, Western
endothelial nitric oxide synthase
gene expression
heme oxygenase (decyclizing)
heme oxygenase 1
hypertension
Hypertension, Pulmonary - chemically induced
Hypertension, Pulmonary - metabolism
Immunohistochemistry
inducible nitric oxide synthase
Lung - enzymology
Lung - metabolism
lungs
Male
monocrotaline
Monocrotaline - toxicity
nitric oxide synthase
Nitric Oxide Synthase - metabolism
pathophysiology
protein synthesis
Rat Models
Rats
Rats, Sprague-Dawley
Receptor, TIE-2 - metabolism
receptors
temporal variation
Vascular Endothelial Growth Factor A - metabolism
vascular endothelial growth factors
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Summary:Angiogenic factors such as vascular endothelial growth factor (VEGF) are implicated in pulmonary hypertension (PH). However, the pathway of angiogenic factor-mediated pathologic angiogenesis in PH remains unclear. In this study, we evaluated the temporal expression of angiopoietin (Ang) 1, Ang2, and their receptor (Tie2) as well as VEGF, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and heme oxygenase 1 (HO1) in the monocrotaline-induced PH model. Histologic evaluation showed pathologic vascular remodeling in the arteries of lung sections 1 wk after monocrotaline treatment. Protein levels of Ang1, Ang2, eNOS, iNOS, HO1, and VEGF were increased 1 wk after monocrotaline treatment but Tie2 protein levels were decreased 2 wk afterward. These results suggest that Ang2 mediates vascular remodeling in PH by decreasing Tie2 expression. Therefore, the Ang-Tie2 system may play a role in the pathophysiology of PH.
ISSN:1532-0820
2769-819X