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J Appl Physiol 105: 1333-1341, 2008. First published July 3, 2008; doi:10.1152/japplphysiol.90470.2008
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REVIEW

HIGHLIGHTED TOPIC
Physiology of the Aging Vasculature

Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B

Anna Csiszar,1 Mingyi Wang,2 Edward G. Lakatta,2 and Zoltan Ungvari1

1Department of Physiology, New York Medical College, Valhalla, New York; and 2Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland

ABSTRACT

One of the major conceptual advances in our understanding of the pathogenesis of age-associated cardiovascular diseases has been the insight that age-related oxidative stress may promote vascular inflammation even in the absence of traditional risk factors associated with atherogenesis (e.g., hypertension or metabolic diseases). In the present review we summarize recent experimental data suggesting that mitochondrial production of reactive oxygen species, innate immunity, the local TNF-{alpha}-converting enzyme (TACE)-TNF-{alpha}, and the renin-angiotensin system may underlie NF-{kappa}B induction and endothelial activation in aged arteries. The theme that emerges from this review is that multiple proinflammatory pathways converge on NF-{kappa}B in the aged arterial wall, and that the transcriptional activity of NF-{kappa}B is regulated by multiple nuclear factors during aging, including nuclear enzymes poly(ADP-ribose) polymerase (PARP-1) and SIRT-1. We also discuss the possibility that nucleophosmin (NPM or nuclear phosphoprotein B23), a known modulator of the cellular oxidative stress response, may also regulate NF-{kappa}B activity in endothelial cells.

senescence; resveratrol; caloric restriction; poly(ADP-ribose) polymerase; renin-angiotensin system; coronary artery disease; stroke; myocardial infarction


Address for reprint requests and other correspondence: A. Csiszar or Z. Ungvari, Dept. of Physiology, New York Medical College, Valhalla, NY 10595 (e-mail: anna_csiszar{at}nymc.edu; zoltan_ungvari{at}nymc.edu)




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