Vascular effects of the human extracellular superoxide dismutase R213G variant

Yi Chu; Abdullah ALWAHDANI; Shinichiro IIDA; Donald D LUND; Frank M FARACI; Donald D HEISTAD

doi:10.1161/CIRCULATIONAHA.104.531251

Back

Vascular effects of the human extracellular superoxide dismutase R213G variant

Journal article

Open access

Peer reviewed

Vascular effects of the human extracellular superoxide dismutase R213G variant

Yi Chu, Abdullah ALWAHDANI, Shinichiro IIDA, Donald D LUND, Frank M FARACI and Donald D HEISTAD

Circulation (New York, N.Y.), Vol.112(7), pp.1047-1053

2005

DOI: 10.1161/CIRCULATIONAHA.104.531251

PMID: 16087794

Files and links (1)

url

https://doi.org/10.1161/CIRCULATIONAHA.104.531251View

Published (Version of record) Open Access

Abstract

Background— Extracellular superoxide dismutase (ECSOD) is a major extracellular antioxidant enzyme. We have demonstrated that vascular effects of ECSOD require an intact heparin-binding domain. A common genetic variant with a substitution in the heparin-binding domain (ECSODR213G) was reported recently to be associated with ischemic heart disease. The goal of this study was to examine vascular effects of ECSODR213G. Methods and Results— A recombinant adenovirus (Ad) that expresses ECSODR213G was constructed. ECSODR213G and ECSOD proteins bound to collagen type I in vitro, but binding to aorta ex vivo was 10-fold greater with ECSOD than ECSODR213G. Three days after intravenous injection of AdECSODR213G or AdECSOD in spontaneously hypertensive rats (SHR), immunostaining demonstrated binding of ECSOD to carotid arteries and kidneys but minimal binding of ECSODR213G. Binding to aorta and carotid artery was 2.5- to 3-fold greater with ECSOD than ECSODR213G by immunoblotting. Arterial pressure was significantly reduced by AdECSOD but not by AdECSODR213G. Responses to acetylcholine and basal levels of nitric oxide in carotid arteries were impaired in SHR compared with normotensive Wistar-Kyoto rats and were improved after AdECSOD but not AdECSODR213G. Levels of superoxide and nitrotyrosine in aorta were higher in SHR than Wistar-Kyoto rats and were greatly reduced after AdECSOD but not AdECSODR213G. Conclusions— In contrast to ECSOD, ECSODR213G has no significant protective effect on arterial pressure, vascular function, or vascular levels of oxidative stress in SHR. These findings may provide a mechanistic basis for association studies that suggest that human beings carrying ECSODR213G are predisposed to vascular diseases.

Cardiovascular System

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

Blood vessels and receptors

Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous

Pharmacology. Drug treatments

Biological and medical sciences

Medical sciences

Vertebrates: cardiovascular system

Vasodilator agents. Cerebral vasodilators

Blood and lymphatic vessels

Details

Title: Subtitle: Vascular effects of the human extracellular superoxide dismutase R213G variant
Creators: Yi Chu - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Abdullah ALWAHDANI - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Shinichiro IIDA - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Donald D LUND - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Frank M FARACI - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Donald D HEISTAD - Cardiovascular Center and Departments of Internal Medicine, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Circulation (New York, N.Y.), Vol.112(7), pp.1047-1053
DOI: 10.1161/CIRCULATIONAHA.104.531251
PMID: 16087794
NLM abbreviation: Circulation
ISSN: 0009-7322
eISSN: 1524-4539
Publisher: Lippincott Williams & Wilkins; Hagerstown, MD
Language: English
Date published: 2005
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040203302771

Metrics

17 Record Views

65 Times Cited - Web of Science