Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice.

Objective: There are several pathways that mediate the aberrant metabolism of glucose and that might induce greater vascular damage in the setting of diabetes. The polyol pathway mediated by aldose reductase (AR) has been postulated to be one such pathway. However, it has been reported that AR reduces toxic lipid aldehydes and, under some circumstances, might be antiatherogenic.

Aldose reductase and AGE-RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats.

Aging is inevitably accompanied by gradual and irreversible innate endothelial dysfunction. In this study, we tested the hypothesis that accentuation of glucose metabolism via the aldose reductase (AR) pathway contributes to age-related vascular dysfunction. AR protein and activity levels were significantly increased in aged vs.

Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice.

Endothelial dysfunction is a key triggering event in atherosclerosis. Following the entry of lipoproteins into the vessel wall, their rapid modification results in the generation of advanced glycation endproduct epitopes and subsequent infiltration of inflammatory cells. These inflammatory cells release receptor for advanced glycation endproduct (RAGE) ligands, specifically S100/calgranulins and high-mobility group box 1, which sustain vascular injury.

JAK-STAT pathway in cardiac ischemic stress.

In our quest for comprehensive protection of ischemic myocardium, both basic and clinical studies have lead us to examine signal transduction pathways involved in ischemia-reperfusion injury for potential therapeutic targets. In this review, we have highlighted the importance of the JAK-STAT pathway in modulating ischemia-reperfusion injury. The mechanisms linking glucose metabolism, angiotensin II, with JAK-STAT pathway in ischemic injury are explored in this review.

Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice.

Direct evidence that hyperglycemia, rather than concomitant increases in known risk factors, induces atherosclerosis is lacking. Most diabetic mice do not exhibit a higher degree of atherosclerosis unless the development of diabetes is associated with more severe hyperlipidemia. We hypothesized that normal mice were deficient in a gene that accelerated atherosclerosis with diabetes.