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on March 27, 2006

Circulation. 2006
Published online before print March 27, 2006, doi: 10.1161/CIRCULATIONAHA.104.513820
A more recent version of this article appeared on April 4, 2006
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Submitted on June 1, 2004
Revised on January 20, 2006
Accepted on January 27, 2006

Abdominal Aortic Aneurysm Is Associated With High Serum Levels of Tenascin-X and Decreased Aneurysmal Tissue Tenascin-X

Manon C. Zweers PhD, Anita C.T.M. Peeters MD, Sietze Graafsma MD, Steef Kranendonk MD, J. Adam van der Vliet MD, Martin den Heijer PhD, MD*, and Joost Schalkwijk PhD

From the Department of Dermatology (M.C.Z., J.S.), Nijmegen Centre for Molecular Life Sciences, and the Departments of Endocrinology (A.C.T.M.P., M.d.H.), Epidemiology and Biostatistics (M.d.H.), and Surgery (J.A.v.d.V.,), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; and the Departments of Internal Medicine (S.G.) and Surgery (S.K.), TweeSteden Hospital, Tilburg, the Netherlands.

* To whom correspondence should be addressed. E-mail: M.denHeijer{at}endo.umcn.nl.

Background--Tenascin-X is a large extracellular matrix protein that is abundantly expressed in several connective tissues. A 140-kDa C-terminal fragment of tenascin-X is present in human serum. Complete deficiency of tenascin-X is associated with Ehlers-Danlos syndrome, and these patients show major connective tissue alterations in their skin, as well as blood vessel fragility. In this study, we investigated whether tenascin-X is present in normal human aorta and abdominal aortic aneurysm (AAA) tissues and whether an association exists between serum tenascin-X levels and AAA.

Methods and Results--Five normal aortas and 5 AAA tissues were immunostained for tenascin-X and elastin. Tenascin-X was present throughout the entire aorta and was especially abundant near the elastic lamellae, whereas tenascin-X expression was strongly decreased in AAA tissue. Measurement of tenascin-X serum concentration by enzyme-linked immunosorbent assay (ELISA) in 87 AAA patients and 86 controls demonstrated an increasing risk for AAA with increasing tenascin-X serum concentrations. After adjustment for established risk factors, tenascin-X serum concentrations in the highest quartile were associated with a 5-fold increase in risk of AAA (odds ratio, 5.3; 95% confidence interval, 2.0 to 13.8).

Conclusions--Tenascin-X expression is markedly decreased in AAA tissue, and AAA is associated with high serum concentrations of tenascin-X.


Key words: aneurysm • collagen • extracellular matrix • pathology • risk factors




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