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The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity

  • 0Departamento de Fisiología, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, Madrid, Spain.
Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology +

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July 11, 2024

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July 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Galectin-3 and endoplasmic reticulum (ER) stress drive cardiac fibrosis after myocardial infarction (MI), especially in obesity. Inhibiting galectin-3 or ER stress improved heart function and reduced fibrosis in rats.

Area Of Science

  • Cardiovascular Research
  • Biomedical Science
  • Pathophysiology

Background

  • Cardiac fibrosis is a key factor in myocardial infarction (MI) progression and adverse cardiac remodeling.
  • Galectin-3 is implicated in cardiovascular disease, but its role in obesity-associated MI and fibrosis requires further elucidation.
  • Endoplasmic reticulum (ER) stress is increasingly recognized as a contributor to cardiac dysfunction and fibrosis.

Purpose Of The Study

  • To investigate the association between galectin-3, ER stress, and cardiac fibrosis in patients and an animal model of MI.
  • To evaluate the therapeutic potential of inhibiting galectin-3 and ER stress in mitigating cardiac fibrosis and dysfunction post-MI in obese rats.

Main Methods

  • Human patients with acute MI were assessed for circulating galectin-3 levels, cardiac structure, and function.
  • Obese rats subjected to MI were treated with modified citrus pectin (MCP) to inhibit galectin-3 or 4-phenylbutyric acid (4-PBA) to inhibit ER stress.
  • Cardiac fibrosis, galectin-3 expression, ER stress markers, autophagic flux, and cardiac function were evaluated in animal models.

Main Results

  • Overweight-obese MI patients exhibited higher galectin-3, extracellular volume, and LV infarct size, with lower LVEF compared to normal-weight patients.
  • Obese-infarcted rats showed increased cardiac fibrosis, galectin-3 expression, and ER stress activation, alongside reduced autophagic flux and impaired cardiac function.
  • Treatment with MCP or 4-PBA significantly reduced cardiac fibrosis, galectin-3 levels, ER stress, and improved cardiac function and autophagic flux in obese rats.

Conclusions

  • Galectin-3 plays a significant role in diffuse cardiac fibrosis associated with MI in the context of obesity.
  • ER stress activation is closely linked with galectin-3 in promoting cardiac fibrosis and dysfunction post-MI.
  • Targeting galectin-3 and ER stress pathways offers a promising therapeutic strategy for managing MI complications, particularly in obese individuals.

Keywords:

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