Therapeutic effect and mechanism of rBMSCs/F92A-Cav1 on PAH rats
XU Cong
XIA Peng
YANG Hongli
TANG Wenqiang
PAN Li
WANG Lanhua
CHEN Shuangfeng
ZHANG Yingxin
WANG Lexin
CHEN Haiying
Abstract：To investigate the therapeutic effect and mechanism of Caveolin-1 (Cav1) mutant to F92A-Cav1 modified rat bone marrow mesenchymal stem cells (rBMSCs/F92A-Cav1) on rats with pulmonary hypertension (PAH).Methods PAH was induced by intraperitoneal injection of 1% monocrotaline (MCT, 60 mg/kg) in adult male Wistar rats.The PAH rats were randomly divided into four groups (10 rats/group) after 2 weeks of MCT injection: PAH group (only MCT), Cav1 group (transduced with LV-Cav1 modified rBMSCs), F92A-Cav1 group (transduced with LV-F92A-Cav1modified rBMSCs), and the control group.Gene modified rBMSCs (1×106/ml) were transplanted into PAH rats in each group by tail vein injection.After 3 weeks of transplantation, the percentage of media wall thickness (MT%) and right ventricular hypertrophy index (RVHI) were evaluated by Image-Pro Plus 6 software, serum NO concentration was checked by Griess method, and the expression of phosphoinositide 3-kinase(PI3K) and protein kinase B (AKT) was detected by Western blotting.Results MT%, RVHI, PI3K and AKT was all increased but NO was decreased in the PAH group as compared with that of the control group(P<0.05 or P<0.01).Compared with the PAH group, MT%, RVHI, PI3K and AKT was decreased but NO was increased in the Cav1 and F92A-Cav1 groups, especially in the F92A-Cav1 group (P<0.01).Conclusion F92A-Cav1 can abrogate the inhibitory effect of wild-type Cav1 on eNOS and promote the release of NO, then inhibit the activation of PI3K/Akt signaling pathway and thus exert its therapeutic effect on PAH rats.
Keywords：pulmonary arterial hypertensionCaveolin-1mesenchymal stem cellsrats
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 20-23 )