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.

Aldose reductase and AGE-RAGE pathways: key players in myocardial ischemic injury / M. Kaneko, L. Bucciarelli, Y. Hwang, L. Lee, S. Yan, A. Schmidt, R. Ramasamy. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - 1043:(2005 Jun), pp. 702-709. (Intervento presentato al 8. convegno International Symposium on the Maillard Reaction : August, 29th - September, 1st tenutosi a Charleston nel 2004) [10.1196/annals.1333.081].

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

L. Bucciarelli
Secondo
;
2005

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.
AGEs; Aldose reductase; Ischemia reperfusion injury; Myocardial ischemia; Polyol pathway; RAGE
Settore MED/13 - Endocrinologia
giu-2005
University of South Caroline
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1045710
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