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Aldose Reductase: An Emerging Target for Development of Interventions for Diabetic Cardiovascular Complications

Sravya Jannapureddy1, Mira Sharma1, Gautham Yepuri1

  • 1Diabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, NYU Grossman School of Medicine, New York, NY, United States.

Frontiers in Endocrinology
|March 29, 2021
PubMed

Insights

High blood glucose activates the aldose reductase (AR) pathway, worsening diabetic cardiovascular disease. Inhibiting AR shows promise for protecting hearts and treating atherosclerosis in diabetes patients.

Area of Science:

  • Cardiology
  • Endocrinology
  • Biochemistry

Background:

  • Diabetes is a major risk factor for cardiovascular disease (CVD), yet standard CVD treatments offer limited benefits to diabetic patients.
  • The expanding diabetes epidemic necessitates the development of diabetes-specific therapies to modify disease progression.
  • Elevated blood glucose levels activate the aldose reductase (AR) pathway, impacting cardiovascular cells.

Purpose of the Study:

  • To review the role of aldose reductase (AR) in the development and progression of diabetic cardiovascular complications.
  • To summarize the current understanding of AR inhibitors in clinical trials for managing diabetic cardiovascular disease.

Main Methods:

  • Review of existing literature, including human studies and animal models.
  • Analysis of genetic studies linking aldose reductase gene (ALD2) single nucleotide polymorphisms (SNPs) to diabetic complications.
  • Examination of research on the effects of AR flux in diabetic hearts and atherosclerosis models.

Main Results:

  • Increased AR flux in the heart is observed in diabetes and ischemia, with AR inhibition demonstrating protective effects against ischemia-reperfusion injury in animal models.
  • Human AR expression accelerates atherosclerotic plaque progression and hinders regression in mouse models of diabetic atherosclerosis.
  • Genetic variations in the ALD2 gene are associated with cardiorenal complications in diabetic individuals.

Conclusions:

  • Aldose reductase (AR) plays a significant role in the pathogenesis of diabetic cardiovascular disease.
  • AR inhibitors represent a potential therapeutic strategy for managing cardiovascular complications in diabetes.
  • Further clinical evaluation of AR inhibitors is warranted to confirm their efficacy and safety.
Keywords:
aldose reductasealdose reductase inhibitorcardiovascular diabetic complicationscardiovascular diseasediabeteshyperglycemiapolyol pathway

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