Expression of hypoxia-inducible factor-1 alpha and endothelin-1 gene in hypoxic pulmonary hypertension.
OBJECTIVE
To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and endothelin-1 (ET-1) gene in hypoxic pulmonary hypertension (HPH).


METHODS
The animal model of HPH was replicated. The elastic fiber staining was applied to show the intraacinar pulmonary artery (IAPA). Radioimmunoassay (RIA) and in situ hybridization (ISH) were used for detection of HIF-1a and. ET-1.


RESULTS
ISH showed that HIF-1alpha mRNA was expressed in the IAPA of all hypoxic rat. The expression was stronger in the H14 d (0.256 9 +/- 0.046 8) and H28 d (0.225 8 +/- 0.045 3) groups than in the H5 d (0.1455 +/- 0.072 2) and control (0.110 9 +/- 0.022 4) groups (P < 0.05), the expression of ET-1 mRNA in the H14 d (0.412 2 +/- 0.078 3) and H28 d (0.368 4 +/- 0.072 9) groups was also stronger than that in the H5 d (0.201 7 +/- 0.034 9) and control (0.185 5 +/- 0.036 1) groups (P < 0.05). The amount of ET-1 in pulmonary arteial blood in the H14 d [(158.78 +/- 25.14) pg/ml] and H28 d [(142.93 +/- 23.38) pg/ml] groups was significantly higher than that in the H5 d [(79.68 +/- 12.54) pg/ml] and control [(65.37 +/- 10.82) pg/ml] groups (P < 0.05). The mean pulmonary arterial pressure (mPAP) in the H14 d [(34.0 +/- 5.8) mm Hg] and H 28 d [(29.0 +/- 4.7) mm Hg] groups was markedly higher than that in the H5 d [(19.0 +/- 3.5) mm Hg] and control [(17.0 +/- 2.8) mm Hg] groups (P < 0.05). A positive rank correlation existed between the mPAP and the amount of ET-1 (rs = 0.747, P < 0.05).


CONCLUSIONS
Expression of HIF-1alpha and ET-1 mRNA in IAPA increase under long-term hypoxic condition and both show consistent expression, indicating that the expression of HIF-1a and ET-1 gene contribute to pathogenesis of HPH.
Ao
Qilin
Q
Department of Pathoology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China. aoqilin@263.net
Hao
Chunrong
C
Xiong
Mi
M
Wang
Dixun
D
D000818:Animals; D019332:Endothelin-1 / Q000235:genetics*; D015870:Gene Expression; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D000860:Hypoxia / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics*
D019332:Endothelin-1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D014157:Transcription Factors