LAUSR

Pulmonary arterial hypertension (PAH) is a life-threatening disorder characterized by Abrelevated mean pulmonary arterial pressure (mPAP >20 mmHg) as a consequence of enhanced pulmonary vascular resistance (PVR) (Simonneau et al., 2019). Pulmonary artery vasoconstriction and vascular remodeling greatly contribute to a sustained elevation of PVR and pulmonary arterial pressure (PAP) in patients with PAH. Abnormal upregulation of cytoplasmic Ca2+ in pulmonary artery smooth muscle cells plays a central role. However, calcium channel blocker (CCB) is only effective in 10% of patients with a positive acute vascular response and it is rapidly becoming resistant to treatment (Galie et al., 2015). The main pharmacological effect of CCB is the inhibition of L-type voltage-dependent calcium channels (VDCC), thus inhibiting receptor-operated Ca2+ channels (ROCC) which mainly regulates Ca2+ influx and consequently blocks the process of vasoconstriction (Ng and Gurney, 2001). It is known that the main components of store-operated calcium channel (SOCC) are the members of the transient receptor potential channel (TRPC) family (Somlyo and Somlyo, Nature, 1994, 372, 231–236; Birnbaumer et al., Proc Natl Acad Sci United States, 1996, 93, 15,195–15202; Zhu et al., Cell, 1996, 85, 661–671; Zitt et al., Neuron, 1996, 16, 1,189–1,196) and pulmonary artery smooth muscle cell (PASMC) mainly expressed TRPC1, TRPC2, TRPC4, TRPC5, and TRPC6 (Golovina et al., Am J Physiol Heart Circ Physiol, 2001, 280, H746–755) . A mountain of studies (Golovina et al., Am J Physiol Heart Circ Physiol, 2001, 280, H746–755; Sweeney et al., Am J Physiol Lung Cell Mol Physiol, 2002, 283, L144–155; Fantozzi et al., Am J Physiol Lung Cell Mol Physiol, 2003, 285, L1233–1,245) has suggested that transient receptor potential channel played an important role in the development of PH, but few of them can be used as an effective therapeutic target. We find it difficult to target TRPC as a treatment target because of its wide implication. Du et al. (Du et al., FASEB J, 2014, 28, 4677–4685) described that TRPC1 can act as a component that senses shear stress. It is generally recognized that shear stress, one of the most significant intravascular mechanics, plays a significant role in the contraction and remodeling of the vasculature. Piezo1 is a mechanosensitive, non-selective cationic ion channel protein. In specific, the Piezo channels are activated by shear stress in local blood flow and by cell membrane stretch (Douguet et al., 2019). We, therefore, suggest that Piezo1 is the initiating factor in the disturbance of Ca homeostasis in PASMC in some types of PAH, for example, chronic thromboembolic pulmonary hypertension (CTEPH) and congenital heart diseaseassociated PAH. The primary roles of Piezo1 in vascular mechanical transduction have been identified as sensing blood flow shear stress and fostering vascular development (Li OPEN ACCESS