Spexin Diminishes Atrial Fibrillation Vulnerability by Acting on Galanin Receptor 2.

CREB IK1 SLN atrial fibrillation galanin receptors spexin

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
10 May 2024
Historique:
medline: 10 5 2024
pubmed: 10 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms. Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile, Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

Sections du résumé

BACKGROUND UNASSIGNED
G protein-coupled receptors play a critical role in atrial fibrillation (AF). Spexin is a novel ligand of galanin receptors (GALRs). In this study, we investigated the regulation of spexin and GALRs on AF and the underlying mechanisms.
METHODS UNASSIGNED
Global spexin knockout (SPX-KO) and cardiomyocyte-specific GALRs knockout (GALR-cKO) mice underwent burst pacing electrical stimulation. Optical mapping was used to determine atrial conduction velocity and action potential duration. Atrial myocyte action potential duration and inward rectifying K
RESULTS UNASSIGNED
Spexin plasma levels in patients with AF were lower than those in subjects without AF, and knockout of spexin increased AF susceptibility in mice. In the atrium of SPX-KO mice, potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) and sarcolipin (SLN) were upregulated; meanwhile,
CONCLUSIONS UNASSIGNED
Spexin reduces atrial fibrillation susceptibility by inhibiting CREB phosphorylation and thus downregulating KCNJ2 and SLN transcription by GALR2 receptor. The spexin/GALR2/CREB signaling pathway represents a novel therapeutic avenue in the development of agents against atrial fibrillation.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.123.067517 PMID: 38726666
pubmed: 38726666
doi: 10.1161/CIRCULATIONAHA.123.067517
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Desheng Li (D)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).
ORCID: 0000-0002-4884-745X

Yang Liu (Y)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).

Changzhu Li (C)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Zhiwen Zhou (Z)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Kangyi Gao (K)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Hairong Ba (H)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Jiming Yang (J)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).
ORCID: 0000-0003-0007-5152

Genlong Xue (G)

Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, China (G.X.).

Dechun Yin (D)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).
ORCID: 0000-0002-7057-9340

Xinbo Zhao (X)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).

Kewei Shen (K)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Lingmin Zhang (L)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Jialiang Li (J)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).
ORCID: 0000-0001-7177-6648

Chenhong Li (C)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Jiahui Song (J)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Lexin Zhao (L)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Yao Pei (Y)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Lina Xuan (L)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Yang Zhang (Y)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).
ORCID: 0000-0002-6680-3098

Yanjie Lu (Y)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Zhi-Ren Zhang (ZR)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).
NHC Key Laboratory of Cell Transplantation (Z.-R.Z., Y. Li, Z.P.).
ORCID: 0000-0003-1324-6934

Baofeng Yang (B)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).

Yue Li (Y)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).
NHC Key Laboratory of Cell Transplantation (Z.-R.Z., Y. Li, Z.P.).
ORCID: 0000-0002-7727-905X

Zhenwei Pan (Z)

National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, International Cooperation Base for Major Cardiovascular Diseases in Cold Regions, China), College of Pharmacy (D.L., Changzhu Li, Z.Z., K.G., H.B., J.Y., K.S., L. Zhang, J.L., Chenhong Li, J.S., L. Zhao, Y.P., L.X., Y.Z., Y. Lu, B.Y., Z.P.).
National Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Cardiology (Y. Liu, D.Y., X.Z., Z.-R.Z., Y. Li, Z.P.).
NHC Key Laboratory of Cell Transplantation (Z.-R.Z., Y. Li, Z.P.).
First Affiliated Hospital, Harbin Medical University, China. Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019 Research Unit 070, Harbin, China (Z.P.).
ORCID: 0000-0002-1011-0954

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