2. Academic Validation
  3. Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway

Increased sympathetic outflow induced by emotional stress aggravates myocardial ischemia-reperfusion injury via activation of TLR7/MyD88/IRF5 signaling pathway

  • Inflamm Res. 2023 Mar 18. doi: 10.1007/s00011-023-01708-0.
Zhihao Liu # 1 2 3 4 5 6 7,  Zihan Liu # 1 2 3 4 5 6 7,  Huixin Zhou # 1 2 3 4 5 6 7,  Yuyang Zhou 1 2 3 4 5 6 7,  Xiao Xu 1 2 3 4 5 6 7,  Zeyan Li 1 2 3 4 5 6 7,  Fuding Guo 1 2 3 4 5 6 7,  Yuhong Wang 1 2 3 4 5 6 7,  Zhen Zhou 1 2 3 4 5 6 7,  Liping Zhou 1 2 3 4 5 6 7,  Yueyi Wang 1 2 3 4 5 6 7,  Xiaoya Zhou 8 9 10 11 12 13 14,  Hao Xia 15 16 17 18 19 20 21,  Hong Jiang 22 23 24 25 26 27 28
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, People's Republic of China.
  • 2 Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
  • 3 Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, 430060, People's Republic of China.
  • 4 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430060, People's Republic of China.
  • 5 Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China.
  • 6 Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China.
  • 7 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.
  • 8 Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, People's Republic of China. [email protected].
  • 9 Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 10 Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, 430060, People's Republic of China. [email protected].
  • 11 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 12 Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 13 Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China. [email protected].
  • 14 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 15 Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, People's Republic of China. [email protected].
  • 16 Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 17 Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, 430060, People's Republic of China. [email protected].
  • 18 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 19 Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 20 Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China. [email protected].
  • 21 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 22 Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei, People's Republic of China. [email protected].
  • 23 Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 24 Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan, 430060, People's Republic of China. [email protected].
  • 25 Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 26 Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • 27 Hubei Key Laboratory of Cardiology, Wuhan, 430060, People's Republic of China. [email protected].
  • 28 Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China. [email protected].
  • # Contributed equally.
PMID: 36933018 DOI: 10.1007/s00011-023-01708-0
Abstract

Background and objective: Emotional stress substantially increases the risk of ischemic cardiovascular diseases. Previous study indicates that sympathetic outflow is increased under emotional stress. We aim to investigate the role of increased sympathetic outflow induced by emotional stress in myocardial ischemia-reperfusion (I/R) injury, and explore the underlying mechanisms.

Methods and results: We used Designer Receptors Exclusively Activated by Designer Drugs technique to activate the ventromedial hypothalamus (VMH), a critical emotion-related nucleus. The results revealed that emotional stress stimulated by VMH activation increased sympathetic outflow, enhanced blood pressure, aggravated myocardial I/R injury, and exacerbated infarct size. The RNA-seq and molecular detection demonstrated that Toll-like Receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88), interferon regulatory factor 5 (IRF5), and downstream inflammatory markers in cardiomyocytes were significantly upregulated. Emotional stress-induced sympathetic outflow further exacerbated the disorder of the TLR7/MyD88/IRF5 inflammatory signaling pathway. While inhibition of the signaling pathway partially alleviated myocardial I/R injury aggravated by emotional stress-induced sympathetic outflow.

Conclusion: Increased sympathetic outflow induced by emotional stress activates TLR7/MyD88/IRF5 signaling pathway, ultimately aggravating I/R injury.

Keywords

Brain–heart interaction; Myocardial ischemia–reperfusion; Sympathetic outflow; Toll-like receptor 7; Ventromedial hypothalamus.

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