Transient receptor potential vanilloid 4 (TRPV4) in neutrophils enhances myocardial ischemia/reperfusion injury.


Journal

Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628

Informations de publication

Date de publication:
01 09 2023
Historique:
received: 24 10 2022
revised: 07 05 2023
accepted: 12 05 2023
medline: 4 9 2023
pubmed: 26 5 2023
entrez: 26 5 2023
Statut: ppublish

Résumé

The Ca2+-permeable TRPV4 cation channel is expressed in neutrophils and contributes to myocardial ischemia/reperfusion injury. Here we tested the hypotheses that TRPV4 promotes neutrophil activation and subsequently aggregates myocardial ischemia/reperfusion injury. TRPV4 protein was confirmed in neutrophils, and its function was assessed by the current and intracellular Ca2+ concentration elevations evoked by TRPV4 agonists. Furthermore, TRPV4 agonists dose-dependently promoted migration toward fMLP, reactive oxygen species production, and myeloperoxidase release, which were prevented by pretreatment with a selective TRPV4 antagonist, in neutrophils from TRPV4 knockout mice, Ca2+-free medium, or BAPTA-AM + Ca2+-free medium. Blockade of TRPV4 also inhibited the effects of commonly used neutrophil activators fMLP and PMA. Mechanically, TRPV4 regulated neutrophil activation, particularly reactive oxygen species production, by affecting PKCα, P38, and AKT via Ca2+ signaling. In addition, isolated hearts infused with neutrophils from wild-type mice showed additional myocardial ischemia/reperfusion injuries but not those infused with TRPV4 knockout. Our study reveals that TRPV4-mediated neutrophil activation enhances myocardial ischemia/reperfusion injury, and it might be a novel therapeutic target for myocardial ischemia/reperfusion injury and other neutrophil-mediated inflammatory diseases.

Identifiants

pubmed: 37232941
pii: 7180258
doi: 10.1093/jleuko/qiad063
doi:

Substances chimiques

Reactive Oxygen Species 0
TRPV Cation Channels 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

266-279

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Yuwei Wu (Y)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Kai Lu (K)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University, 183 Yiling Avenue, Yichang 443003, China.

Yang Lu (Y)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Jie Liao (J)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Shaoshao Zhang (S)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Shuaitao Yang (S)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Ning Zhao (N)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Qian Dong (Q)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Lei Chen (L)

Department of Physiology, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing 211166, China.

Qiongfeng Wu (Q)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Yimei Du (Y)

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

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