Effect of rBMSCs/Cav1F92A on pulmonary vascular proliferation lesions in PAH rats
YANG Hongli
PAN Li
XU Cong
TANG Wenqiang
WANG Lei
XIA Peng
CHEN Shuangfeng
WANG Lexin
CHEN Haiying
Abstract：Objective To investigate the effect of Cav1F92A modified rat bone marrow mesenchymal stem cells (rBMSCs/Cav1F92A) on pulmonary vascular proliferation lesions in rats with pulmonary arterial hypertension (PAH) and to explore its possible mechanism.Methods Forty Wister rats were randomly divided into the Cav1, Cav1F92A, PAH, and normal control groups with 10 in each.PAH was induced by intraperitoneal injection of 1% monocrotaline (MCT) (60 mg/kg) in adult male Wistar rats in the Cav1, Cav1F92A, and PAH groups.Meanwhile, rats in the control group were injected with the same volume of normal saline.At week 2 after PAH models were established, 1 mL rBMSCs/Cav1 and 1 mL rBMSCs/Cav1F92A (1×106/mL) were transplantated into the rats of the Cav1 and Cav1F92A groups by tail vein injection, while rats in the PAH group were not treated.Rats in each group were sacrificed and the lung tissues were dissected after 3 weeks of transplantation.The changes of pulmonary vascular lumen and vessel wall thickness were observed under microscope by HE staining.The gene expression of Bbc3, B cell translocation of lung tissue 2 (Btg2), Dab2, peroxisome proliferator activated receptor (Ppard), and Rock1 and leucine rich alpha-2 glycoprotein 1 (Lrg1) in the lung tissues was detected by using real-time quantitative PCR.The protein expression of endothelin 1 (ET-1) and smooth muscle myosin heavy chain (Myocardin) was investigated by Western blotting.Results Compared with the normal control group, the pulmonary vascular lumen became narrow, nearly closed, and the vascular wall became hyperplastic and hypertrophic significantly in the PAH group.Compared with the PAH group, the thickening degree of pulmonary vascular wall was reduced in the Cav1 and Cav1F92A groups but more obviously decreased in the Cav1F92A group, but the pulmonary vascular wall was thicker than that in the normal control group.Compared with the normal control group, the relative mRNA expression of Bbc3 and Btg2 in the lung tissues of the PAH group decreased, but the mRNA expression of Dab2, Ppard, Rock1, and Lrg1 relative, and the protein expression of ET-1 and Myocardin increased (all P<0.01).Compared with the PAH group, the Bbc3 and Btg2 mRNA expression increased but Dab2, Ppard, Rock1 and Lrg1mRNA expression decreased in the Cav1 and Cav1F92A groups, especially in the Cav1F92A group (P<0.05 or P<0.01);the Bbc3 and Btg2 mRNA expression in the lung tissues was higher than that in the PAH and Cav1 groups (P<0.05 or P<0.01).Compared with the PAH and Cav1 groups, the protein expression of ET-1 and Myocardin in the lung tissues decreased in the Cav1F92A group (both P<0.01).Conclusion rBMSCs/Cav1F92A can effectively alleviate vascular proliferative lesions in PAH rats by up-regulating the expression of Bbc3 and Btg2, Ppard, Dab2, and Rock1, and down-regulating the expression of ET-1 and Myocardin, and thus inhibiting the vascular smooth muscle cell proliferation, fibrosis, and vascular contraction.
Keywords：pulmonary arterial hypertensionCaveolin-1endothelial nitric oxide synthasenitric oxidebone marrow mesenchymal 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：5( 13-16,前插1 )