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Glucose-6-phosphate dehydrogenase: a novel therapeutic target in cardiovascular diseases

Sachin A Gupte1

  • 1University of South Alabama, College of Medicine, Department of Biochemistry & Molecular Biology, MSB 2310, 307 University Boulevard North, Mobile, AL 36688, USA. sagupte@usouthal.edu

Current Opinion in Investigational Drugs (London, England : 2000)
|August 30, 2008
PubMed

Insights

Altered glucose metabolism, particularly involving glucose-6-phosphate dehydrogenase (G6PD), contributes to vascular dysfunction in diseases like diabetes and heart failure. Targeting G6PD may offer new therapeutic strategies for these conditions.

Area of Science:

  • Biochemistry
  • Cardiovascular Science
  • Metabolic Disease

Background:

  • Vascular dysfunction is a primary driver of morbidity and mortality globally, linked to diabetes, heart failure, and pulmonary hypertension.
  • Altered glucose metabolism, specifically the enzyme glucose-6-phosphate dehydrogenase (G6PD), is implicated as a common factor in these vascular diseases.
  • Elevated G6PD activity and NADPH levels correlate with endothelial and vascular dysfunction in diabetes and heart failure.

Purpose of the Study:

  • To review the role of glucose-6-phosphate dehydrogenase (G6PD) in vascular dysfunction across various diseases.
  • To discuss the implications of G6PD-derived NADPH in oxidative stress and disease pathogenesis.
  • To highlight the need for novel therapeutic strategies targeting G6PD and to review existing investigational inhibitors.

Main Methods:

  • Review of existing literature on glucose-6-phosphate dehydrogenase (G6PD) in vascular dysfunction.
  • Analysis of G6PD's role in diabetes, heart failure, pulmonary hypertension, and smooth muscle hypertrophy.
  • Discussion of G6PD-derived NADPH's contribution to oxidative stress via NADPH oxidase.

Main Results:

  • Increased G6PD activity and expression are observed in diabetes and heart failure models.
  • Inhibition of G6PD demonstrates potential in ameliorating chronic hypoxic pulmonary hypertension.
  • G6PD mediates angiotensin II-induced smooth muscle hypertrophy and contributes to atherosclerosis development.

Conclusions:

  • Glucose-6-phosphate dehydrogenase (G6PD) plays a significant role in the pathogenesis of vascular dysfunction in multiple diseases.
  • G6PD-derived NADPH contributes to oxidative stress, a key factor in these conditions.
  • Development of specific drugs or genetic approaches targeting G6PD is warranted for clinical investigation and treatment.

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