Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation

Concentric pulmonary vascular wall thickening due partially to increased PASMC proliferation contributes to elevating PVR in pulmonary hypertension (PH) patients. While pulmonary vasoconstriction may be an early contributor to increasing PVR, the transition of contractile PASMCs to proliferative PASMCs may play an important role in developing and progressing pulmonary vascular remodelling in PH. A rise in cytosolic Ca2+ concentration ([Ca2+]cyt) is a trigger for PASMC contraction and proliferation. Here, the study reports that the upregulation of Piezo1, a mechanosensitive cation channel, is involved in the contractile-to-proliferative phenotypic transition of PASMCs and the development of pulmonary vascular remodelling. By comparing freshly isolated PA (contractile PASMCs) and primary cultured PASMCs in growth medium (proliferative PASMCs), the study found that Piezo1, Notch2/3 and CaSR protein levels were significantly higher in proliferative PASMCs than in contractile PASMCs. Upregulated Piezo1 may play a critical role in PASMC phenotypic transition and PASMC proliferation. Upregulation of Piezo1 in proliferative PASMCs may likely be required to provide sufficient Ca2+ to assure nuclear/cell division and PASMC proliferation, contributing to the development and progression of pulmonary vascular remodelling in PH.