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

Michiyo Kaneko, Loredana Bucciarelli, Yuying C. Hwang, Larisee Lee, Shi Fang Yan, Ann Marie Schmidt, Ravichandran Ramasamy

Research output: Contribution to journalArticle

Abstract

Cardiovascular disease represents the major cause of morbidity and mortality in patients with diabetes mellitus. The impact of cardiac disease includes increased sensitivity of diabetic myocardium to ischemic episodes and diabetic cardiomyopathy, manifested as a subnormal functional response of the diabetic heart independent of coronary artery disease. In this context, we were to our knowledge the first to demonstrate that diabetes increases glucose flux via the first and key enzyme, aldose reductase, of the polyol pathway, resulting in impaired glycolysis under normoxic and ischemic conditions in diabetic myocardium. Our laboratory has been investigating the role of the polyol pathway in mediating myocardial ischemic injury in diabetics. Furthermore, the influence of the aldose reductase pathway in facilitating generation of key potent glycating compounds has led us to investigate the impact of advanced glycation end products (AGEs) in myocardial ischemic injury in diabetics. The potent impact of increased flux via the aldose reductase pathway and the increased AGE interactions with its receptor (RAGE) resulting in cardiac dysfunction will be discussed in this chapter.

Original languageEnglish
Pages (from-to)702-709
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1043
DOIs
Publication statusPublished - 2005

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Keywords

  • AGEs
  • Aldose reductase
  • Ischemia reperfusion injury
  • Myocardial ischemia
  • Polyol pathway
  • RAGE

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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