EGLN1 inhibition reverses angiogenesis impairment in hyperglycemia by activating autophagy

Fengli Hu1, Zheng Li1, Ying Li1

  • 1Cardiology department, Second Hospital of Hebei Medical University, Shijiazhuang, China.

Scientific Reports
|October 14, 2025
PubMed

Insights

Diabetic cardiomyopathy impairs blood vessel growth in the heart. Inhibiting EGLN1 protein activates cell repair, offering a new therapeutic target for diabetic heart disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Diabetes Research

Background:

  • Cardiovascular complications are the leading cause of mortality in diabetes mellitus (DM).
  • Diabetic cardiomyopathy (DCM) presents a unique challenge, characterized by diastolic dysfunction, hypertrophy, and fibrosis, with impaired myocardial angiogenesis contributing to poor outcomes.
  • Current therapies for restoring angiogenesis in DCM are limited.

Purpose of the Study:

  • To identify novel molecular targets for treating DCM.
  • To investigate the role of egl-9 family hypoxia inducible factor 1 (EGLN1) in myocardial angiogenesis in DCM.
  • To explore the potential of EGLN1 inhibition as a therapeutic strategy.

Main Methods:

  • Bioinformatic analysis of public databases to identify differentially expressed genes in DCM.
  • Establishment of a diabetic mouse model and hyperglycemic endothelial cell cultures.
  • Assessment of EGLN1 expression, angiogenesis, and autophagy markers (LC3-II/LC3-I, P62).

Main Results:

  • EGLN1 was significantly upregulated in diabetic mice and correlated with impaired angiogenesis.
  • EGLN1 inhibition in vitro attenuated high glucose-induced endothelial dysfunction.
  • EGLN1 inhibition activated autophagy pathways, indicated by increased LC3-II/LC3-I ratios and decreased P62 levels.

Conclusions:

  • EGLN1 is a novel regulator of myocardial angiogenesis in diabetic cardiomyopathy.
  • Inhibition of EGLN1 ameliorates high glucose-induced endothelial dysfunction by activating autophagy.
  • Targeting EGLN1 and activating autophagy presents a potential therapeutic avenue for diabetic cardiovascular complications.

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