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(Circulation. 2006;113:1702-1707.)
© 2006 American Heart Association, Inc.

Vascular Medicine

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^*; 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.

Correspondence to Martin den Heijer, Department of Endocrinology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail M.denHeijer{at}endo.umcn.nl

Received June 1, 2004; de novo received October 12, 2004; revision received January 20, 2006; accepted January 27, 2006.

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.

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