| Center for Pulmonary Vascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China |
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Abstract Intracellular vesicular transport is shown to be dysfunctional in pulmonary arterial hypertension (PAH). However, the expression of intracellular vesicular transport proteins in PAH remains unclear. To elucidate the possible role of these proteins in the development of PAH, the changes in the expressions of N-ethyl-maleimide-sensitive factor (NSF), 锟斤拷-soluble NSF attachment protein (锟斤拷-SNAP), synaptosome-associated membrane protein 23 (SNAP23), type 2 bone morphogenetic receptor (BMPR2), caveolin-1 (cav-1), and endothelial nitric oxide synthase (eNOS) were examined in lung tissues of monocrotaline (MCT)-treated rats by real-time polymerase chain reaction and western blot analysis. In addition, caspase-3, also examined by western blot analysis, was used as an indicator of apoptosis. Our data showed that during the development of PAH, the expressions of NSF, 锟斤拷-SNAP, and SNAP23 were significantly increased before pulmonary arterial pressure started to increase and then significantly decreased after PAH was established. The expressions of BMPR2 and eNOS were similar to those of NSF, 锟斤拷-SNAP, and SNAP23; however, the expression of cav-1 was down-regulated after MCT treatment. Caspase-3 expression was increased after exposure to MCT. In conclusion, the expressions of NSF, 锟斤拷-SNAP, and SNPA23 changed greatly during the onset of PAH, which was accompanied by abnormal expressions of BMPR2, cav-1, and eNOS, as well as an increase in apoptosis. Thus, changes in NSF, 锟斤拷-SNAP, and SNAP23 expressions appear to be mechanistically associated with the development of PAH in MCT-treated rats.
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