1. Academic Validation
  2. Microglia-Mediated Neuroimmune Response Regulates Cardiac Remodeling After Myocardial Infarction

Microglia-Mediated Neuroimmune Response Regulates Cardiac Remodeling After Myocardial Infarction

  • J Am Heart Assoc. 2023 Jun 20;12(12):e029053. doi: 10.1161/JAHA.122.029053.
Menglong Wang 1 2 3 Jishou Zhang 1 2 3 Zheng Yin 1 2 3 Wen Ding 4 Mengmeng Zhao 1 2 3 Jianfang Liu 1 2 3 Yao Xu 1 2 3 Shuwan Xu 1 2 3 Wei Pan 1 2 3 Cheng Wei 1 2 3 Hong Jiang 1 2 3 Jun Wan 1 2 3
Affiliations

Affiliations

  • 1 Department of Cardiology Renmin Hospital of Wuhan University Wuhan China.
  • 2 Cardiovascular Research Institute Wuhan University Wuhan China.
  • 3 Hubei Key Laboratory of Cardiology Wuhan China.
  • 4 Department of Radiology The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou China.
Abstract

Background Sympathetic hyperactivity contributes to pathological remodeling after myocardial infarction (MI). However, the mechanisms underlying the increase in sympathetic activity remain unknown. Microglia are the predominant immune cells in the central nervous system and can regulate sympathetic neuron activity through neuroimmune response in the hypothalamic paraventricular nucleus. The present study aimed to investigate whether microglia-mediated neuroimmune response can regulate sympathetic activity and cardiac remodeling after MI. Methods and Results PLX3397 (pexidartinib) was used to deplete central microglia via intragastric injection or intracerebroventricular injection. After that, MI was induced by ligation of the left anterior descending coronary artery. Our study showed that MI resulted in the activation of microglia in the paraventricular nucleus. Microglia depletion, which was induced by PLX3397 treatment via intragastric injection or intracerebroventricular injection, improved cardiac function, reduced infarction size, and attenuated cardiomyocyte Apoptosis, fibrosis, pathological electrical remodeling, and myocardial inflammation after MI. Mechanistically, these protective effects were associated with an attenuated neuroimmune response in the paraventricular nucleus, which contributed to the decrease of sympathetic activity and attenuation of sympathetic remodeling in the heart. However, intragastric injection with PLX3397 obviously depleted macrophages and induced neutrophil and T-lymphocyte disorders in the heart, blood, and spleen. Conclusions Microglia depletion in the central nervous system attenuates pathological cardiac remodeling after MI by inhibiting neuroimmune response and sympathetic activity. Intragastric administration of PLX3397 leads to serious deleterious effects in peripheral immune cells, especially macrophages, which should be a cause for concern in animal experiments and clinical practice.

Keywords

cardiac remodeling; microglia; myocardial infarction; neuroimmune response.

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