Background: Piezo1 is a mechanosensitive cation channel membrane protein, which can be activated by various mechanical stimuli, promote cellular calcium influx, and participate in pulmonary vascular remodeling and vascular development. However, how Piezo1 can participate in the development of pulmonary hypertension (PH) in different types of pulmonary vascular cells is still unclear. In this study, the left pulmonary artery ligation (LPAL) model was used to simulate high blood flow PH in rats to investigate the role of Piezo1 in pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (ECs) involved in high blood flow-induced PH. Methods: Adult male rats were randomly divided into SHAM operation group (SHAM) and left pulmonary artery ligation group (LPAL-PH). Hemodynamic evaluation of rats was performed at the 2nd and 5th postoperative weeks, respectively. Pulmonary vascular remodeling, inflammation, proliferation and related protein expression were evaluated by histopathology, Masson staining, immunofluorescence and immunoblotting. Vascular tension and calcium ion imaging were used to evaluate the effects of Piezo1 on cellular calcium ion changes and vasomotor in the model. Results: Compared with the SHAM group, the right ventricular systolic blood pressure and right ventricular index were significantly increased in the LPAL-PH group, and significant pulmonary vascular and right ventricular remodeling occurred at the same time. The diastolic and systolic functions of the pulmonary vasculature were significantly inhibited. Piezo1 expression was abnormally elevated in PASMCS and ECs of LPAL-PH rats, and the former was associated with cytoplasmic Ca2+Concentration ([Ca2+］cyt) was associated with Yes-associated protein (YAP) /TEA domain transcription factor 4 (TEAD4); The latter may be related to transcriptional regulation caused by RELA (p65) and lung inflammation. Conclusion: The study demonstrated that the role of Piezo1 in PASMCs and ECs in LPAL-PH was heterogeneous, and it could activate different cell signaling pathways to jointly promote pulmonary vascular remodeling and endothelial dysfunction in LPAL-PH rats, which provided new insights for the differential regulation of Piezo1 in high blood flow pulmonary vascular diseases.
