Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells from Idiopathic Pulmonary Arterial Hypertension Patients

Jing Liao, Wenju Lu, Yuqin Chen, Xin Duan, Chenting Zhang, Xiaoyun Luo, Ziying Lin, Jiyuan Chen, Shiyun Liu, Han Yan, Yilin Chen, Huazhuo Feng, Dansha Zhou, Xu Chen, Zizhou Zhang, Qifeng Yang, Xinyi Liu, Haiyang Tang, Jing Li, Ayako MakinoJason X.J. Yuan, Nanshan Zhong, Kai Yang, Jian Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Emerging studies have reported the mechanosensitive Piezo1 (piezo type mechanosensitive ion channel component 1) plays essential roles in regulating the vascular tone through mechanistic actions on intracellular calcium homeostasis. However, the specific roles of Piezo1 in pulmonary vessels remain incompletely understood. We aim to investigate whether and how Piezo1 regulates the intracellular calcium homeostasis in human pulmonary arterial smooth muscle cells (PASMCs) under normal and pulmonary arterial hypertension (PAH) conditions. Cultured human PASMCs isolated from both control donors and idiopathic PAH patients were used as cell models. Fura-2 based intracellular calcium imaging was performed to measure the intracellular free calcium concentration ([Ca2+]i). Results showed that activation of Piezo1 by Yoda1 increases [Ca2+]iby inducing both intracellular calcium release from internal calcium stores through the intracellular (intra-) Piezo1 localized at the subcellular organelles, including endoplasmic reticulum/sarcoplasmic reticulum, mitochondria, and nucleus; as well as extracellular calcium influx through the plasma membrane-localized Piezo1 in a mechanism independent of the store-operated calcium entry. Moreover, the Piezo1-mediated increase of [Ca2+]iis linked to increased contraction and proliferation of PASMCs. Yoda1 induces dose-dependent vasocontraction in endothelium-denuded rat intrapulmonary arteries. Significant upregulation and increased activity of Piezo1 were observed in idiopathic PAH-PASMCs versus donor-PASMCs, contributing to the increased [Ca2+]iand excessive proliferation of idiopathic PAH-PASMCs. In summary, Piezo1 mediates the increase of [Ca2+]iby triggering both intracellular calcium release and extracellular influx. The enhanced Piezo1 expression and activity accounts, at least partially, for the abnormally elevated [Ca2+]iand proliferation in idiopathic PAH-PASMCs.

Original languageEnglish (US)
Pages (from-to)1974-1989
Number of pages16
JournalHypertension
DOIs
StateAccepted/In press - 2021

Keywords

  • calcium
  • endothelium
  • homeostasis
  • muscle cells
  • pulmonary arterial hypertension

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint

Dive into the research topics of 'Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells from Idiopathic Pulmonary Arterial Hypertension Patients'. Together they form a unique fingerprint.

Cite this