Document Detail

The role of lysyl oxidase family members in the stabilization of abdominal aortic aneurysms.
MedLine Citation:
PMID:  22904155     Owner:  NLM     Status:  MEDLINE    
Abdominal aortic aneurysms (AAAs) are a major cause of morbidity and mortality in the United States today. We employed a model for AAA development using apolipoprotein E knock out mice fed a high-fat diet and treated with ANG II and β-aminopropionitrile (β-APN) for 4 wk. ANG II induces hypertension and atherosclerotic disease, whereas β-APN inhibits the activity of the lysyl oxidase/ lysyl oxidase-like protein (LOX/LOXL) family members. LOX/LOXL family members crosslink collagen and elastin in the extracellular matrix and therefore contribute to the integrity and stabilization of a healthy vessel wall. In this model, cotreatment with ANG II and β-APN caused a 90% AAA incidence and increased atherosclerotic lesion formation from less than 5% to greater than 25% after 4 wk. In more atheroprotected mouse strains (C57BL/6 and BalbC), cotreatment with ANG II and β-APN caused 50% and 40% AAA incidence, respectively. These data demonstrate the importance of LOX/LOXL to the stability of the vessel wall. Therapeutic strategies to overexpress LOX/LOXL enzymes or to support the crosslinking of soluble matrix proteins in a polymeric scaffold are a promising opportunity to achieve stabilization of AAAs.
Ebony Washington Remus; Robert E O'Donnell; Kathryn Rafferty; Daiana Weiss; Giji Joseph; Katalin Csiszar; Sheri F T Fong; W Robert Taylor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-17
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  303     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2012-12-26     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1067-75     Citation Subset:  IM    
Division of Cardiology Department of Medicine, Emory University School of Medicine Atlanta, Georgia 30322, USA.
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MeSH Terms
Amino Acid Oxidoreductases / genetics,  metabolism*
Aminopropionitrile / pharmacology
Angiotensin II / pharmacology
Aorta, Abdominal / enzymology*
Aortic Aneurysm, Abdominal / enzymology*
Apolipoproteins E / genetics
Atherosclerosis / enzymology*
Diet, High-Fat
Disease Models, Animal
Extracellular Matrix / enzymology
Extracellular Matrix Proteins / genetics,  metabolism*
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Protein-Lysine 6-Oxidase / genetics,  metabolism*
RNA, Messenger / metabolism
Vasoconstrictor Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Apolipoproteins E; 0/Extracellular Matrix Proteins; 0/RNA, Messenger; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; 149137-54-2/Lox protein, mouse; 151-18-8/Aminopropionitrile; EC 1.4.-/Amino Acid Oxidoreductases; EC 1.4.3.-/LOXL3 protein, mouse; EC 1.4.3.-/Loxl1 protein, mouse; EC 1.4.3.-/Loxl2 protein, mouse; EC 1.4.3.-/Loxl4 protein, mouse; EC 6-Oxidase

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