Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial dysfunction

Sean P Didion; Dale A Kinzenbaw; Pamela E Fegan; Lisa A Didion; Frank M Faraci

doi:10.1161/01.STR.0000132764.06878.c5

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Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial dysfunction

Journal article

Open access

Peer reviewed

Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial dysfunction

Sean P Didion, Dale A Kinzenbaw, Pamela E Fegan, Lisa A Didion and Frank M Faraci

Stroke (1970), Vol.35(8), pp.1963-1967

08/2004

DOI: 10.1161/01.STR.0000132764.06878.c5

PMID: 15218160

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Abstract

Inflammation is thought to be a major contributor to carotid artery disease. Lipopolysaccharide (LPS) activates inflammatory mechanisms thought to contribute to endothelial dysfunction by mechanisms that are not well defined. The goal of this study was to determine whether overexpression of CuZn-SOD protects against LPS-induced increases in superoxide and endothelial dysfunction. Carotid arteries from CuZn-SOD transgenic (SOD-Tg) and nontransgenic (non-Tg) littermates were examined in vitro. Superoxide levels were measured using lucigenin-enhanced chemiluminescence. In non-Tg mice, LPS (0.5 microg/mL for 22 hours) produced marked impairment of vasorelaxation in response to the endothelium-dependent dilator acetylcholine (ACh). For example, 100 micromol/L ACh relaxed carotid arteries from non-Tg mice by 86+/-6% and 38+/-8% after treatment with vehicle and LPS, respectively. In contrast, LPS did not significantly impair responses of carotid artery to ACh in SOD-Tg mice, and LPS had no effect on relaxation responses to the endothelium-independent dilator nitroprusside in carotid artery from non-Tg or SOD-Tg mice. LPS-induced increases in superoxide, as measured using lucigenin-enhanced chemiluminescence, were higher in vessels from non-Tg mice than from SOD-Tg mice. These results indicate that LPS increases superoxide and impairs endothelium-dependent relaxation. Overexpression of the CuZn isoform of SOD effectively prevents LPS-induced oxidative stress and endothelial dysfunction in the carotid artery.

Oxidative Stress

Lipopolysaccharides - administration & dosage

Nitroprusside - administration & dosage

Mice, Transgenic

Inflammation

Endothelium, Vascular - physiology

Acetylcholine - administration & dosage

Animals

Superoxide Dismutase - physiology

Carotid Arteries - physiology

Superoxides - metabolism

Mice

Vasodilation - drug effects

Vasodilator Agents - administration & dosage

Details

Title: Subtitle: Overexpression of CuZn-SOD prevents lipopolysaccharide-induced endothelial dysfunction
Creators: Sean P Didion - Department of Internal Medicine, Cardiovascular Center, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242-1081, USA
Dale A Kinzenbaw
Pamela E Fegan
Lisa A Didion
Frank M Faraci
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.35(8), pp.1963-1967
DOI: 10.1161/01.STR.0000132764.06878.c5
PMID: 15218160
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
Grant note: HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS DK-25295 / NIDDK NIH HHS
Language: English
Date published: 08/2004
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Teaching and Learning; Internal Medicine
Record Identifier: 9984040318702771

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