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TIME-DEPENDENT BENEFICIAL EFFECT OF CHRONIC POLYPHENOL TREAT- MENT WITH CATECHIN ON ENDOTHELIAL DYSFUNCTION IN AGING MICE

Abstract
A controlled redox environment is essential for vascular cell maturation and function. During aging, an imbalance occurs, leading to endothelial dysfunction. We hypothesized that, according to the concept of hormesis, exposure to physiologic oxidative stress dur- ing the maturation phase of the endothelium will activate protective pathways involved in stress resistance. C57Bl/6 mice were treated with the polyphenol catechin for the last 3 (post-maturation) or 9 months prior study at 12 months of age. Endothelial dysfunction, assessed by acetylcholine-induced dilations of isolated renal arteries, was present at 12 months (P<0.05). Only the 3-month treatment with catechin fully prevented the decline in efficacy and sensitivity to acetylcholine (P<0.05). Splenocytes adhesion to the native endothelium, expression of CD18 and shedding of CD62L and PSGL-1 augmented in 12 months old mice (P<0.05): only 3-month catechin fully normalized adhesion and pre- vented the expression of adhesion molecules on splenocytes (P<0.05). Aging was associat- ed with vascular gene alterations, which were prevented by 3-month catechin treatment (P<0.05). In contrast, 9-month catechin further increased COX-2, p22phox and reduced MnSOD (P<0.05). In conclusion, we demonstrate a pivotal role of cellular redox equilibri- um: exposure to physiologic oxidative stress during the maturation phase of the endothelium is essential for its function.
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Date
2012-03-01
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