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Glucose Fluctuations Aggravate Cardiac Susceptibility to Ischemia/Reperfusion Injury by Modulating MicroRNAs

Shotaro Saito1, Luong Cong Thuc, Yasushi Teshima

  • 1Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University.

Circulation Journal : Official Journal of the Japanese Circulation Society
|October 27, 2015
PubMed
Abstract

Insights

Glucose fluctuations (GF) worsen heart damage from ischemia/reperfusion in diabetes mellitus (DM) by increasing reactive oxygen species (ROS). Upregulated microRNAs (miRNAs) 200c and 141 contribute to this heightened oxidative stress.

Area of Science:

  • Cardiovascular Research
  • Metabolic Disorders
  • Molecular Biology

Background:

  • Diabetes mellitus (DM) is associated with cardiovascular complications.
  • The impact of glucose fluctuations (GF) on these complications is under investigation.
  • This study examines if GF exacerbate cardiac ischemia/reperfusion (I/R) injury.

Purpose of the Study:

  • To investigate the effect of GF on myocardial susceptibility to ischemia/reperfusion injury in a diabetic rat model.
  • To elucidate the underlying mechanisms, including oxidative stress and microRNA involvement.

Main Methods:

  • Male rats were divided into control, DM, and DM with GF groups.
  • Diabetes was induced by streptozotocin; GF was induced by starvation and insulin.
  • Isolated hearts underwent 20-min ischemia/30-min reperfusion; infarct size and biochemical markers were assessed.

Main Results:

  • Hearts with GF exhibited larger infarct sizes compared to sustained hyperglycemia.
  • GF increased reactive oxygen species (ROS) production and decreased antioxidant enzyme activity.
  • Mitochondrial damage was more severe in GF hearts; miRNA-200c and miRNA-141 were upregulated.
  • Overexpression of these miRNAs mimicked GF effects, while knockdown reduced ROS.

Conclusions:

  • Glucose fluctuations significantly enhance ischemia/reperfusion injury in the diabetic heart.
  • Increased ROS generation is a key mediator of this enhanced injury.
  • Upregulation of miRNA-200c and miRNA-141 is implicated in the elevated ROS levels observed in GF conditions.

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