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Aldose Reductase and AGE‐RAGE Pathways: Key Players in Myocardial Ischemic Injury
Author(s) -
KANEKO MICHIYO,
BUCCIARELLI LOREDANA,
HWANG YUYING C.,
LEE LARISEE,
YAN SHI FANG,
SCHMIDT ANN MARIE,
RAMASAMY RAVICHANDRAN
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.081
Subject(s) - aldose reductase , polyol pathway , medicine , diabetes mellitus , rage (emotion) , coronary artery disease , glycation , diabetic cardiomyopathy , cardiology , context (archaeology) , myocardial infarction , disease , endocrinology , cardiomyopathy , heart failure , biology , paleontology , neuroscience
A bstract : 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.