[The role of bone morphogenetic protein-2 in the pathogenesis of hypoxic pulmonary hypertension].
OBJECTIVE
To investigate the change of bone morphogenetic protein-2 (BMP-2) in the lung tissues of rats with hypoxic pulmonary hypertension (HPH) and the role of BMP in the apoptosis of endothelial cells exposed to hypoxia.


METHODS
Twenty male Wistar rats were randomly divided into two groups, the HPH group and the control group, 10 rats in each group. The HPH model was established by placing the rats in an isobaric chamber [O(2) = (10 +/- 0.5)%] for three weeks. The distribution of BMP-2 in pulmonary tissues was observed by using streptavidin peroxidase method (SP), and the morphologic changes of pulmonary arterioles and the integrated optical density (IA) of BMP-2 were determined by image analysis. The effect of Noggin (a blocking agent of BMP) on the apoptosis of hypoxic cultivated human umbilical vein endothelial cells (HUVEC) was assayed by flow cytometers.


RESULTS
Compared to the control group, pulmonary artery hypertension was evident in the hypoxic rats: mPAP was 16.3 +/- 0.5 mm Hg (1 mm Hg = 0.133 kPa) vs (29.5 +/- 0.9) mm Hg, P < 0.01. In the hypoxic rats, the pulmonary arteriolar wall thickened significantly; WT% was (16 +/- 5)% vs (27 +/- 7)%, and WA% was (54 +/- 11)% vs (80 +/- 8)%, both P < 0.01. The distribution of BMP-2 was mainly in the pulmonary arteriolar walls. The IA of BMP-2 significantly increased (6124 +/- 1199 vs 13 463 +/- 5755, P < 0.01), and showed a positive linear relationship to WT% and WA% respectively (WT%: r = 0.744 P < 0.01; WA%: r = 0.693 P < 0.01). Hypoxia induced apoptosis of HUVEC; the apoptosis rate was increased from 6% to 14% and 25% after exposure to hypoxia for 24 h and 48 h respectively. The HUVEC apoptosis rate induced by hypoxia was reduced by Noggin to 11.91% (24 h) and 15.01% (48 h).


CONCLUSIONS
Chronic hypoxia induced an increased expression of BMP-2, and a blocking agent of BMP inhibited the apoptosis of endothelial cells induced by hypoxia. It suggests that BMP may play an important role in the pathogenesis of hypoxic pulmonary hypertension.
Yang
Ying
Y
Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
Cheng
De-Yun
DY
Fan
Li-Li
LL
Yang
Yan-Juan
YJ
Mu
Mao
M
Chen
Wen-Bin
WB
D000818:Animals; D017209:Apoptosis; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014471:Umbilical Veins / Q000166:cytology
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2