Therapeutic effect of mesenchymal stem cell on pulmonary hypertension and its influence on tumor necrosis factor α/nuclear factor of activated T cells

Abstract

Objective To illustrate that tumor necrosis factor-α(TNF-α)/ nuclear factor of activated T cells pathway is the main function way that mesenchymal stem cells(MSC) inhibit proliferation of pulmonary vascular smooth muscle cells during treating pulmonary hypertension(PH). Methods MSC from human umbilical cord was used to treat PH rat models induced by monocrotaline.Rats were divided into the control group, the PH model group and the MSC group.The general conditions of the rats were observed.Haemodynamics was detected.Pathological sections and immunohistochemistry method were used to detect the lung structure and tissue changes.Changing conditions of TNF-α/NFAT were detected. Results Compared with rats in the PH model group, the general conditions of the MSC group tended to be normal evidently: the right ventricular systolic pressure (RVSP) dropped [(30.37±3.13) mmHg vs.(47.90±3.45) mmHg, 1 mmHg=0.133 kPa], the aortic pressure (MAoP) increased [(115.03±16.01) mmHg vs.(92.78±16.28 mmHg)], the thickening condition of arterial intima-media was evidently relieved [(17.22±1.21)% vs.(31.68±2.26)%], the plasma TNF-α level decreased obviously [(842±76) ng/L vs.(245±24) ng/L], and the lung tissue TNF-α level decreased (0.172±0.024 vs.0.248±0.051), and all the differences were statistically significant (all P<0.05). The activation of pulmonary artery NFATc2 in the MSC treatment group was apparently inhibited. Conclusions MSC therapy may perform the treating effect in PH by inhibiting the over-proliferation of inflammation related pulmonary vascular smooth muscle cells via TNF-α/NFAT pathway. Key words: Mesenchymal stem cell; Pulmonary hypertension; Tumor necrosis factor; Nuclear factor of activated T cells