Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging.

Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Research Abstract Details 

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Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Abstract Text:

Anna Csiszar,Nazar Labinskyy,Kira Smith,Aracelie Rivera,Zsuzsanna Orosz,Zoltan Ungvari,

Vascular aging is associated with dysregulation of tumor necrosis factor (TNF)-alpha expression. TNF-alpha is a master regulator of vascular proatherogenic phenotypic changes, and it has been linked to endothelial dysfunction and apoptosis. To test the hypothesis that anti-TNF-alpha treatment exerts vasculoprotective effects in aging, aged (29 months old) F344 rats were treated with etanercept (1 mg/kg/week for 4 weeks), which binds and inactivates TNF-alpha. In aged carotid arteries, relaxations to acetylcholine were decreased, and endothelial O2* production was increased (as shown by dihydroethidine fluorescence measurements). Etanercept treatment significantly improved responses to acetylcholine and decreased vascular NAD(P)H oxidase activity and expression. In aged carotid and coronary arteries, there were increases in DNA fragmentation rate and caspase 3/7 activity (indicating an increased rate of apoptotic cell death), which were attenuated by etanercept treatment. In aged vessels, there was an up-regulation of inflammatory markers, including inducible nitric-oxide synthase and intercellular adhesion molecule-1, which was decreased by etanercept treatment. In carotid arteries of young animals, recombinant TNF-alpha elicited endothelial dysfunction, oxidative stress, and increased apoptosis and proinflammatory gene expression, mimicking many of the symptoms of vascular aging. Thus, we propose that anti-TNF-alpha treatment exerts anti-aging vasculoprotective effects.

Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Publishing Authors By Initials

A Csiszar,N Labinskyy,K Smith,A Rivera,Z Orosz,Z Ungvari,

For similar vasodilation research abstracts see: vasodilation research

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Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The American journal of pathology

VOLUME: 170

Page Numbers: 388-98

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 3

MONTH: Jan

YEAR: 2007

Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Information

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LANGUAGE: eng

NlmUniqueID: 370502

Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Keywords Mesh Terms:

KEYWORDS: Vasodilation

MESH TERMS: drug effects

Chemical & Substance for Abstract: Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Information

Substance Name: NADPH Oxidase

Registry Number: EC 1.6.3.1

Grant and Affiliation Information for Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging.

AFFILIATION: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. anna_csiszar@nymc.edu

Country: United States

AGENCY: United States PHS

GRANT: P043023

ACRONYM: HL

MEDLINETA: Am J Pathol

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