Aldose reductase and cardiovascular diseases, creating human-like diabetic
complications in an experimental model.
Authors Ramasamy R, Goldberg IJ
Submitted By Ira Goldberg on 5/2/2011
Status Published
Journal Circulation research
Year 2010
Date Published 5/14/2010
Volume : Pages 106 : 1449 - 1458
PubMed Reference 20466987
Abstract Hyperglycemia and reduced insulin actions affect many biological processes. One
theory is that aberrant metabolism of glucose via several pathways including the
polyol pathway causes cellular toxicity. Aldose reductase (AR) is a
multifunctional enzyme that reduces aldehydes. Under diabetic conditions AR
converts glucose into sorbitol, which is then converted to fructose. This
article reviews the biology and pathobiology of AR actions. AR expression varies
considerably among species. In humans and rats, the higher level of AR
expression is associated with toxicity. Flux via AR is increased by ischemia and
its inhibition during ischemia reperfusion reduces injury. However, similar
pharmacological effects are not observed in mice unless they express a human AR
transgene. This is because mice have much lower levels of AR expression,
probably insufficient to generate toxic byproducts. Human AR expression in LDL
receptor knockout mice exacerbates vascular disease, but only under diabetic
conditions. In contrast, a recent report suggests that genetic ablation of AR
increased atherosclerosis and increased hydroxynonenal in arteries. It was
hypothesized that AR knockout prevented reduction of toxic aldehydes. Like many
in vivo effects found in genetically manipulated animals, interpretation
requires the reproduction of human-like physiology. For AR, this will require
tissue specific expression of AR in sites and at levels that approximate those
in humans.

Investigators with authorship
Ira GoldbergNew York University School of Medicine