[The expression and possible role of SENP1 in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension].
OBJECTIVE
To investigate the dynamic expression and role of SENP1 (SUMO-specific proteases-1) in the pulmonary vascular wall of rat during the development of hypoxic pulmonary hypertension (HPH).


METHODS
Forty adult male Wistar rats were randomly divided into 5 groups (n = 8), and exposed to normoxia (Control group) or exposed to hypoxia for 3, 7, 14 or 21 d, respectively. The HPH models were established by normobaric intermittent hypoxia. Mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI), and vessel morphometry were measured. Reverse transcriptase-polymerase chain reaction(RT-PCR) and in situ hybridization were used to determine the mRNA expression of SENP1. Immunohistochemistry and Western blot were used to determine the protein expression of SENP1.


RESULTS
The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 d of hypoxia exposure. Pulmonary vascular remodeling in pulmonary arterioles significantly increased after 14 d of hypoxia. The level of mPAP in hypoxic rats increased significantly after 7 d of hypoxia, reached its peak after 14 d of hypoxic exposure. RVHI was markedly increased after 14 d of hypoxia. In situ hybridization and immunohistochemical analysis showed that SENP1 mRNA and protein were positively stained in control. SENP1 mRNA expression had little changes after exposure to hypoxia compared with the control, however, SENP1 protein expression was declined gradually after 7 d of hypoxia. The results of RT-PCR and Western blot showed that the same dynamic expression of SENP1 mRNA and protein in lung tissues of rats. Linear correlation analysis showed that SENP1 protein were negatively correlated with mPAP, pulmonary vascular remodeling index and RVHI.


CONCLUSIONS
Under chronic hypoxia, SENP1 protein can be degradated. The dynamic expression of SENP1 protein may play a role in implicating in the development of HPH.
Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410016, China.
Hua
H
Tian
Ai-Guo
AG
Dai
Dai-Yan
DY
Fu
Rui-Cheng
RC
Hu
Li-Ming
LM
Zhu
D000818:Animals; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D008297:Male; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C000630128:SENP1 protein, rat