. 2022 Oct:218:52-63.

doi: 10.1016/j.thromres.2022.08.006. Epub 2022 Aug 17.

Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

Jiyuan Chen¹, Jinrui Miao², Dansha Zhou³, Jing Liao³, Ziyi Wang³, Ziying Lin³, Chenting Zhang³, Xiaoyun Luo³, Yi Li², Xiang Li³, Shiyun Liu³, Yue Xing³, Zizhou Zhang³, Manjia Zhao⁴, Sophia Parmisano⁴, Yuqin Chen³, Jason X-J Yuan⁴, Kai Yang⁵, Dejun Sun⁶, Jian Wang⁷

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA.
² State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Inner Mongolia People's Hospital Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, Hohhot, Inner Mongolia, China.
³ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
⁴ Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA.
⁵ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: kyang28@pku.edu.cn.
⁶ Inner Mongolia People's Hospital Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, Hohhot, Inner Mongolia, China. Electronic address: nmg_sdj@163.com.
⁷ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: jiw037@health.ucsd.edu.

PMID: 35988445
DOI: 10.1016/j.thromres.2022.08.006

Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

Jiyuan Chen et al. Thromb Res. 2022 Oct.

. 2022 Oct:218:52-63.

doi: 10.1016/j.thromres.2022.08.006. Epub 2022 Aug 17.

Authors

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA.
² State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Inner Mongolia People's Hospital Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, Hohhot, Inner Mongolia, China.
³ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
⁴ Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA.
⁵ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: kyang28@pku.edu.cn.
⁶ Inner Mongolia People's Hospital Key Laboratory of National Health Commission for the Diagnosis & Treatment of COPD, Hohhot, Inner Mongolia, China. Electronic address: nmg_sdj@163.com.
⁷ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: jiw037@health.ucsd.edu.

PMID: 35988445
DOI: 10.1016/j.thromres.2022.08.006

Abstract

Introduction: Piezo1 is an important mechanosensitive channel implicated in vascular remodeling. However, the role of Piezo1 in different types of vascular cells during the development of pulmonary hypertension (PH) induced by high shear stress is largely unknown.

Materials and methods: We used a rat PH model established by left pulmonary artery ligation (LPAL, for 2-5 weeks), which mimics the high flow and hemodynamic stress, to study Piezo1 contribution to pulmonary vascular remodeling.

Results: Right ventricular systolic pressure (RVSP), a surrogate measure for pulmonary arterial systolic pressure, and right ventricular wall thickness, a measure for right ventricular hypertrophy, were significantly increased in LPAL rats compared with Sham-control (SHAM) rats. Rats in LPAL-5w groups developed remarkable pulmonary vascular remodeling, while phenylephrine-induced contraction and acetylcholine-induced relaxation were both significantly inhibited in these rats. Upregulation of Piezo1, in association with increase in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt), was observed in pulmonary arterial smooth muscle cells (PASMCs) from LPAL-2w and LPAL-5w rats in comparison to the SHAM controls. Piezo1 upregulation in PASMCs from LPAL rats was directly related to Yes-associated protein (YAP)/ TEA domain transcription factor 4 (TEAD4). Piezo1 expression was also upregulated in the whole-lung tissue of LPAL rats. The endothelial upregulation of Piezo1 was related to transcriptional regulation by RELA (p65) and lung inflammation.

Conclusion: The upregulation of Piezo1 in both PASMCs and ECs coordinates with each other via different cell signaling pathways to cause pulmonary vascular remodeling in LPAL-PH rats, providing novel insights into the cell-type specific pathogenic roles of Piezo1 in shear stress-associated experimental PH.

Keywords: Endothelial cell; Piezo1; Pulmonary hypertension; Shear stress; Smooth muscle cell.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

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Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

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