RESUMO
Objective To investigate the role and mechanism of transforming growth factor-β2 (TGF-β2) on regulating the phenotype transformation of vascular smooth muscle cells (SMC) during the wall remodeling after venous thrombosis. Methods Human umbilical vein smooth muscle cells (HVSMCs) were treated with different concentration (0, 1, 10, 20 ng/ml) of TGF-β2 for 24 hours, or treated with 10 ng/ml TGF-β2 at different time points (0, 2, 6, 24 h). RT-PCR was performed to detect the mRNA expressions of phenotype markers (contractile type: α-SMA and Elastin; synthetic type: Col1A1 and Col1A2). SD rat models of inferior vena cava thrombosis (IVCT) were established. Rats were randomly divided into sham surgery group (n=5), thrombus group (n=9) and TGF-β2 experimental group (n=5). The successful establishment of rat model was confirmed by HE and Masson staining of vein wall tissues on 4 and 7 days after modelling. At the 14th day after modelling, IVCT rats were locally treated with hydrogel containing TGF-β2 10 ng per rat for 24 hours. RT-PCR was used to detect the expression of SMC phenotypic marker mRNA in the vein wall of each group. Results TGF-β2 up-regulated mRNA expressions of both contractile and synthetic markers in HVSMCs in a dose- and time-dependent manner (P<0.05). Notely, the mRNA expression of contractile markers was more up-regulated than that of synthetic markers. HE and Masson staining showed the acute thrombosis phase 4 days after modelling and the chronic organized thrombus and recanalization 7 days after modelling, confirming the successful establishment of IVCT models. At the 14th day after modelling, compared with the sham surgery group, the mRNA expression in SMC venous wall contractile markers of thrombus group was down-regulated obviously, and was up-regulated markedly in synthetic markers (P<0.05). When TGF-β2 was used to locally treat the thrombus, the expressions of contractile markers mRNA were more significantly up-regulated (P<0.05). Conclusions TGF-β2 may induce the expression of contractile and synthetic markers in HVSMCs, particularly up-regulating the contractile markers. In IVCT rats model, TGF-β2 can significantly up-regulate the mRNA expressions of SMC contraction markers, which is in favour of maintenance of SMC contractile phenotype in the thrombus vein wall.