Abnormal expression of NSF, α-SNAP and SNAP23 in pulmonary arterial hypertension in rats treated with monocrotaline.
BACKGROUND
Recent researches have shown that dysfunctional intracellular vesicular trafficking exists in pulmonary arterial hypertension (PAH). However, the expression of proteins involved in intracellular vesicular trafficking in pulmonary vasculature in PAH remains unclear.


OBJECTIVE
To elucidate possible roles of proteins involved in intracellular vesicular trafficking in the development of PAH in rats treated with monocrotaline, changes in the expression of N-ethyl-maleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP) and synaptosome-associated membrane protein (SNAP) 23 were examined together with expression of caveolin-1 (cav-1), endogenous nitric oxide synthase (eNOS), type 2 bone morphogenetic receptor (BMPR2) and cellular apoptosis.


METHODS
The mRNA expression was investigated by real time-PCR and protein expression by immunoblot method in rat lung. Caspase-3 was used as an indicator of cellular apoptosis and examined by immunoblot method.


RESULTS
During the development of PAH, mRNA and protein expression of NSF, α-SNAP and SNAP23 all significantly increased before pulmonary arterial pressure started to increase, then all significantly decreased when PAH established. The expression of eNOS and BMPR2 changed similarly, while the mRNA and protein of cav-1 both downregulated after monocrotaline treatment. Caspase-3 was also increased after exposure to monocrotaline.


CONCLUSIONS
Since the expression of NSF, α-SNAP and SNAP23 changed greatly during the onset of PAH and accompanied with abnormal expression of eNOS, BMPR2 and cav-1 and with enhanced cellular apoptosis, NSF, α-SNAP and SNAP23 appear to be associated with the development of PAH in rats treated with monocrotaline.
State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's R China.
Hong-Liang
HL
Zhang
State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's R China.
Zhi-Hong
ZH
Liu
State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's R China.
Qin
Q
Luo
State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's R China.
Yong
Y
Wang
State Key Laboratory of Cardiovascular Disease, Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037, People's R China.
Zhi-Hui
ZH
Zhao
Pulmonary arterial hypertension; intracellular vesicular trafficking; monocrotaline