Aldose reductase and AGE-RAGE pathways: key players in myocardial ischemic injury.
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.
Kaneko
Michiyo
M
Division of Surgical Science, P&S 17-401, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA.
Bucciarelli
Loredana
L
Hwang
Yuying C
YC
Lee
Larisee
L
Yan
Shi Fang
SF
Schmidt
Ann Marie
AM
Ramasamy
Ravichandran
R
D000449:Aldehyde Reductase / Q000502:physiology*; D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000449:Aldehyde Reductase