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

• 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
• ISSN: 1532-0820; 2769-819X

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.