Macrophage-targeted overexpression of urokinase causes accelerated atherosclerosis, coronary artery occlusions, and premature death
Language: 
English
Abstract: 

BACKGROUND: Human atherosclerotic lesions contain elevated levels of urokinase plasminogen activator (uPA), expressed predominantly by macrophages. METHODS AND RESULTS: To test the hypothesis that macrophage-expressed uPA contributes to the progression and complications of atherosclerosis, we generated transgenic mice with macrophage-targeted overexpression of uPA. The uPA transgene was bred into the apolipoprotein E-null background, and transgenic mice and nontransgenic littermate controls were fed an atherogenic diet. uPA-transgenic mice had significantly elevated uPA activity in the atherosclerotic artery wall, of a magnitude similar to elevations reported in atherosclerotic human arteries. Compared with littermate controls, uPA-transgenic mice had accelerated atherosclerosis, dilated aortic roots, occlusive proximal coronary artery disease, myocardial infarcts, and early mortality. CONCLUSIONS: These data support the hypothesis that overexpression of uPA by artery wall macrophages is atherogenic and suggest that uPA inhibitors might be therapeutically useful.

Author(s): 
Cozen, Aaron E.
Moriwaki, Hideaki
Kremen, Michal
DeYoung, Mary Beth
Dichek, HelÈn L.
Slezicki, Katherine I.
Young, Stephen G.
VÈniant, Murielle
Dichek, David A.
Item Type: 
Journal Article
Publication Title: 
Circulation
Journal Abbreviation: 
Circulation
Publication Date: 
5/4/2004
Publication Year: 
2004
Pages: 
2129-2135
Volume: 
109
Issue: 
17
ISSN: 
1524-4539
DOI: 
10.1161/01.CIR.0000127369.24127.03
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 15096455

Turabian/Chicago Citation

Aaron E. Cozen, Hideaki Moriwaki, Michal Kremen, Mary Beth DeYoung, HelÈn L. Dichek, Katherine I. Slezicki, Stephen G. Young, Murielle VÈniant and David A. Dichek. 5/4/2004. "Macrophage-targeted overexpression of urokinase causes accelerated atherosclerosis, coronary artery occlusions, and premature death." Circulation 109: 17: 2129-2135. 10.1161/01.CIR.0000127369.24127.03.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1161/01.CIR.0000127369.24127.03 | issn = 1524-4539 | volume = 109 | pages = 2129-2135 | last = Cozen | first = Aaron E. | coauthors = Moriwaki, Hideaki, Kremen, Michal, DeYoung, Mary Beth, Dichek, HelÈn L., Slezicki, Katherine I., Young, Stephen G., VÈniant, Murielle, Dichek, David A. | title = Macrophage-targeted overexpression of urokinase causes accelerated atherosclerosis, coronary artery occlusions, and premature death | journal = Circulation | date = 5/4/2004 | pmid = | pmc = }} </ref>