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A GLP-1 receptor agonist semaglutide attenuates cardiac microvascular injury in HFD/STZ-induced diabetic mice

Xinye Wang1, Xiaoting Wang2, Hong Zhuang1

  • 1Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, PR China.

European Journal of Pharmacology
|December 4, 2025
PubMed

Insights

Semaglutide treatment protected against diabetes-induced cardiac microvascular injury in mice by preserving structure and density. It works through multiple mechanisms, including reducing inflammation and oxidative stress.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Pharmacology

Background:

  • Diabetes complications, including cardiac microvascular injury, increase major adverse cardiovascular events.
  • Semaglutide, a GLP-1 receptor agonist, offers cardiovascular benefits beyond glycemic control.
  • The specific effects of semaglutide on diabetes-induced coronary microvascular injury are not fully understood.

Purpose of the Study:

  • To investigate the impact of semaglutide on diabetes-induced cardiac microvascular injury.
  • To elucidate the underlying mechanisms by which semaglutide exerts its protective effects.

Main Methods:

  • A mouse model of diabetes (streptozotocin and high-fat diet) was used, followed by semaglutide treatment.
  • Cardiac microvascular structure and density were assessed using scanning electron microscopy and CD31 immunofluorescence.
  • Pathways involved in oxidative stress, inflammation, and apoptosis were analyzed via TUNEL staining, Western blotting, and RT-qPCR.

Main Results:

  • Diabetes disrupted cardiac microvascular structure and density, which semaglutide attenuated.
  • Semaglutide reduced advanced glycation end products (AGEs).
  • Semaglutide activated the Nrf2/HO-1/NQO1 pathway, inhibited the MCP-1/CCR2a/NF-κB pathway, reduced inflammatory cytokines, and decreased apoptosis.

Conclusions:

  • Semaglutide treatment mitigates diabetes-related cardiac microvascular injury.
  • Mechanisms include preserving microvascular structure and density, inhibiting perivascular fibrosis, and attenuating inflammation, oxidative stress, and apoptosis.
  • Early and sustained semaglutide administration is beneficial for cardiac microvascular health in diabetes.
Abstract

Keywords:
ApoptosisCardiac microvascular injuryInflammatoryOxidative stressSemaglutide

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