title: Inflammation and endothelial dysfunction during aging: role of NF-kappaB.
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-kappaB induction and endothelial activation in aged arteries. The theme that emerges from this review is that multiple proinflammatory pathways converge on NF-kappaB in the aged arterial wall, and that the transcriptional activity of NF-kappaB 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-kappaB activity in endothelial cells.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. anna_csiszar@nymc.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Mingyi
authors.initials: M
authors.lastname: Wang
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B