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Aldose reductase and AGE-RAGE pathways: key players in myocardial ischemic injury

Michiyo Kaneko1, Loredana Bucciarelli, Yuying C Hwang

  • 1Division of Surgical Science, P&S 17-401, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA.

Annals of the New York Academy of Sciences
|July 23, 2005
PubMed

Insights

Diabetes impairs heart function by increasing glucose metabolism through the polyol pathway, specifically aldose reductase. This leads to reduced glycolysis and worsened cardiac outcomes during ischemia in diabetic patients.

Area of Science:

  • Cardiology
  • Diabetology
  • Biochemistry

Background:

  • Cardiovascular disease is a leading cause of death in diabetes mellitus patients.
  • Diabetic cardiomyopathy and increased myocardial sensitivity to ischemia are significant complications.
  • The polyol pathway's role in diabetic cardiac complications is under investigation.

Purpose of the Study:

  • To investigate the role of the polyol pathway, particularly aldose reductase, in diabetic myocardial dysfunction.
  • To examine the impact of advanced glycation end products (AGEs) on myocardial ischemic injury in diabetes.

Main Methods:

  • Demonstration of increased glucose flux via aldose reductase in diabetic myocardium.
  • Assessment of glycolysis under normoxic and ischemic conditions.
  • Investigation of AGEs and receptor for AGEs (RAGE) interactions.

Main Results:

  • Diabetes increases glucose flux through aldose reductase in the myocardium.
  • This increased flux impairs glycolysis in diabetic hearts, both in normal and ischemic conditions.
  • Elevated AGEs and RAGE interactions contribute to cardiac dysfunction.

Conclusions:

  • The polyol pathway, via aldose reductase, plays a critical role in diabetic heart disease.
  • Increased aldose reductase activity and AGEs/RAGE signaling contribute to cardiac dysfunction in diabetes.
  • Targeting the polyol pathway may offer therapeutic potential for diabetic cardiovascular complications.

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