MicroRNA153 induces apoptosis by targeting NFATc3 to improve vascular remodeling in pulmonary hypertension
Background The present study aimed to investigate the effect of microRNA153 (miRNA153) on pulmonary hypertension (PH). Methods PH was induced by a single subcutaneous injection of sugen5416 (SU5416) combined with hypoxia exposure for 3 weeks (SuHx) in rats, while pulmonary arterial smooth muscle cel...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-11-01
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| Series: | Clinical and Experimental Hypertension |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10641963.2022.2140810 |
| Summary: | Background The present study aimed to investigate the effect of microRNA153 (miRNA153) on pulmonary hypertension (PH). Methods PH was induced by a single subcutaneous injection of sugen5416 (SU5416) combined with hypoxia exposure for 3 weeks (SuHx) in rats, while pulmonary arterial smooth muscle cells (PASMCs) obtained from rats were exposed to hypoxia to establish an in vitro model. Through observing the characteristic hemodynamic index in rats and by analyzing the physiological function, vascular remodeling and right ventricular hypertrophy were identified. The regulatory effects of miRNA153 on the nuclear factor of activated T cell isoform c3 (NFATc3) were measured by RT-qPCR, western blot, and immunofluorescence. Cell apoptosis was evaluated by flow cytometry. Results The miRNA153 expression was reduced and unclear translation of NFATc3 was increased in both the in vivo and in vitro models of PH. In vivo, the pulmonary arterial pressure, right ventricle/(left ventricle + interventricular septum) (RV/(LV+S)), and media vascular thickness were increased in rats with PH; however, all these parameters were suppressed by prophylactic administration of miRNA153agomir. The upregulation of NFATc3 and downregulation of the potassium voltage-gated channel subfamily A member 5 (Kv1.5) were also reversed by transfection with miRNA153agomir. In vitro, miRNA153 increased the level of Kv1.5 in hypoxic PASMCs by targeting NFATc3 and inhibiting their proliferation and apoptosis resistance. Conclusion Our results confirmed that the therapeutic administration of miRNA153 promotes apoptosis and inhibits the proliferation of PASMCs to ameliorate PH, and that the NFATc3/Kv1.5 channel pathway may be involved in this process. |
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| ISSN: | 1064-1963 1525-6006 |