Carbon Monoxide Alleviates Cardiomyocyte Pyroptosis in Diabetic Cardiomyopathy by Downregulating the IL-33/ST2L Axis

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Chunjie Jiang1,2, Ping Zhu1, Ping Yao2

  • 1Jinan University Affiliated Guangzhou Red Cross Hospital, Guangzhou, China.

Immunity, Inflammation and Disease
|August 24, 2025
PubMed
Abstract

Insights

Carbon monoxide (CO) alleviates diabetic cardiomyopathy by reducing cardiomyocyte pyroptosis through the IL-33/ST2L pathway. This study demonstrates CO

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Diabetology

Background:

  • Diabetic cardiomyopathy (DCM) involves cardiomyocyte pyroptosis.
  • The IL-33/ST2L axis is implicated in cardiac dysfunction.
  • Carbon monoxide (CO) has potential therapeutic properties.

Purpose of the Study:

  • To investigate if CO can mitigate cardiomyocyte pyroptosis in DCM.
  • To determine the role of the IL-33/ST2L axis in CO's effects on DCM.
  • To explore CO's therapeutic potential for diabetic heart disease.

Main Methods:

  • Established a diabetic mouse model and treated with CO-releasing molecule-2 (CORM-2).
  • Utilized in vitro studies with high glucose (HG)-treated cardiomyocytes.
  • Assessed cardiac function, protein expression (IL-33, ST2L, pyroptosis markers).

Main Results:

  • High glucose induced pyroptosis and elevated IL-33/ST2L in cardiomyocytes.
  • DCM mice exhibited impaired cardiac function and increased pyroptosis markers.
  • CORM-2 treatment improved cardiac function and reduced pyroptosis by downregulating IL-33/ST2L.

Conclusions:

  • CO inhibits cardiomyocyte pyroptosis in DCM by downregulating the IL-33/ST2L axis.
  • CO demonstrates therapeutic potential for diabetic cardiomyopathy.
  • Targeting the IL-33/ST2L pathway with CO warrants further investigation.
Keywords:
IL‐33/ST2L axiscarbon monoxidediabetic cardiomyopathypyroptosis

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