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Updated: Sep 12, 2025

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
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Na+,-K+-ATPase Deficiency Exacerbates Cardiac Fibrosis via Promoting ERRα-Mediated Myocardial Cell Injury and

Ting Lei1, Tao Liu1,2, Yutong Liu2

  • 1Department of Clinical Laboratory, Xi'an People's Hospital (Xi'an Fourth Hospital), 710004 Xi'an, Shaanxi, China.

Frontiers in Bioscience (Landmark Edition)
|August 6, 2025
PubMed

Insights

Na+, K+-ATPase (NKA) α1 deficiency worsens cardiac fibrosis by increasing inflammation and cell death. Targeting the NKAα1 DR-region may offer a novel therapeutic strategy for heart disease.

Area of Science:

  • Cardiovascular Research
  • Cell Biology
  • Immunology

Background:

  • Inflammation is a key driver of tissue fibrosis.
  • Na+, K+-ATPase (NKA) α1 deficiency impairs mitochondrial function and cardiac remodeling.
  • This study investigates the link between inflammation and NKAα1 deficiency in cardiac fibrosis.

Purpose of the Study:

  • To elucidate the role of NKAα1 deficiency in inflammation-driven cardiac fibrosis.
  • To understand the mechanisms underlying NKAα1 deficiency-induced cardiac remodeling.
  • To identify potential therapeutic targets for cardiac fibrosis.

Main Methods:

  • Utilized a mouse model with NKAα1 haploinsufficiency subjected to isoproterenol (ISO) challenge.
  • Performed histopathology, electron microscopy, RT-qPCR, immunoblotting, and ELISA.
  • Employed a cell co-culture system to study cell interactions.

Main Results:

  • NKAα1 deficiency exacerbated ISO-induced cardiac fibrosis, macrophage infiltration, and inflammatory markers.
  • NKAα1 deficiency accelerated cardiomyocyte death and amplified intercellular crosstalk, promoting inflammation and fibrosis.
  • Estrogen-related receptor α (ERRα) mediated cardiomyocyte death and IL-18 release; a DR-region antibody reduced fibrosis.

Conclusions:

  • NKAα1 deficiency exacerbates cardiac fibrosis via ERRα-dependent cardiomyocyte death and enhanced cell communication.
  • NKAα1 deficiency facilitates crosstalk between cardiomyocytes, macrophages, and fibroblasts, driving fibrosis.
  • NKAα1 and its DR-region are potential therapeutic targets for cardiac fibrosis.
Abstract

Keywords:
NKAfibrosisinflammationisoproterenolmacrophagesmitochondria

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