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 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.
Cho
Yu Ji
YJ
Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Han
Jae Yoon
JY
Lee
Sang Gab
SG
Jeon
Byeong Tak
BT
Choi
Wan Sung
WS
Hwang
Young Sil
YS
Roh
Gu Seob
GS
Lee
Jong Deog
JD
D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D016686:Monocrotaline; D019001:Nitric Oxide Synthase; D042787:Receptor, TIE-2