2. Academic Validation
  3. Macrophage NLRP3 inflammasome mediates the effects of sympathetic nerve on cardiac remodeling in obese rats

Macrophage NLRP3 inflammasome mediates the effects of sympathetic nerve on cardiac remodeling in obese rats

  • Mol Cell Endocrinol. 2025 Jan 15:596:112417. doi: 10.1016/j.mce.2024.112417.
Zhaoqing Xi 1,  Ling Shu 2,  Lingling Xiao 2,  Xuesheng Fang 2,  Mingyan Dai 2,  Jing Wang 3,  Yuan Wu 2,  Junxia Zhang 4,  Mingwei Bao 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; Institute of Model Animal of Wuhan University, Wuhan 430071, China.
  • 2 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
  • 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; State Key Laboratory of Cardiovascular Disease, Heart Failure Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, China.
  • 4 Department of Endocrinology, Taikang Tongji (Wuhan) Hospital, Wuhan, Hubei, 430050, China. Electronic address: zhangjx023@163.com.
  • 5 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address: mbao@whu.edu.cn.
PMID: 39557185 DOI: 10.1016/j.mce.2024.112417
Abstract

Obesity-associated cardiac remodeling is characterized by cardiac sympathetic nerve over-activation and pro-inflammatory macrophage infiltration. We identified norepinephrine (NE), a sympathetic neurotransmitter, as a pro-inflammatory effector to activate macrophage NLRP3 inflammasome, which contributed to cardiac inflammation. In vivo, Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 12 weeks to establish obese rat models. Obese rats exhibited marked cardiac hypertrophy compared to normal rats. The expression of NLRP3 and interleukin (IL)-1β was upregulated, accompanied by CD68+NLRP3+ macrophage infiltration in the hearts of the obese rats. The obese rats also showed increased sympathetic nerve activity. β-adrenergic receptor (AR) inhibition mitigated these changes. In vitro, sympathetic neurotransmitter NE significantly exacerbated palmitic acid (PA)-induced macrophage polarization toward pro-inflammatory type and NLRP3 inflammasome activation in THP-1 macrophages. It was further found that the pro-inflammatory role of NE is dependent on the activation of protein kinase A (PKA) and subsequently inhibition of β-arrestin2, which is an important regulator of the nuclear factor-kappa B (NF-κB) pathway. This study identifies the neuro-immune axis as an important mediator in obesity-associated cardiac remodeling. Targeting the neuro-immune system may open therapeutic opportunities for the treatment of cardiac remodeling in obesity.

Keywords

Cardiac remodeling; Macrophage; NLRP3 inflammasome; Neuro-immune axis; Obesity; Sympathetic nerve.

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