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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:916.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Identification of Soluble Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (sTWEAK) as a Possible Biomarker of Subclinical Atherosclerosis

Luis M. Blanco-Colio; Jose L. Martín-Ventura; Begoña Muñóz-García; Josune Orbe; Jose A. Páramo; Jean-Baptiste Michel; Alberto Ortiz; Olivier Meilhac; Jesús Egido

From Vascular Research Lab (L.M.B.-C., B.M.-G., A.O., J.E.), Fundacion Jimenez Diaz, Autonoma University, Madrid. Spain; INSERM Unit 698 (J.L.M.-V., J.-B.M., O.M.), Cardiovascular Hematology, Bio-Engineering and Remodeling, CHU X-Bichat, Université Paris 7, Paris, France; Atherosclerosis Research Lab (J.O., J.A.P.), Area of Cardiovascular Pathophysiology, Centre for Applied Medical Research, School of Medicine, Pamplona, Spain.

Correspondence to Luis M. Blanco-Colio, PhD, Vascular Research Laboratory, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain. E-mail lblanco{at}fjd.es

Objectives— Assessment of vascular risk in asymptomatic patients and the response to medical therapy is a major challenge for prevention of cardiovascular events. Our aim was to identify proteins differentially released by healthy versus atherosclerotic arterial walls, which could be found in plasma and serve as markers of atherosclerosis.

Methods and Results— We have analyzed supernatants obtained from cultured human carotid plaques and healthy arteries by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry ProteinChip System. Surface-enhanced laser-desorption/ionization analysis unveiled an 18.4-kDa peak released in lower amount by carotid plaques than normal endarteries. This protein was identified as soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). To confirm that sTWEAK was the protein of interest, Western blot and enzyme-linked immunosorbent assay were performed. Both techniques confirmed that sTWEAK levels were decreased in carotid plaque supernatants. Subsequent measurement of sTWEAK in plasma showed a reduced concentration in subjects with carotid stenosis (N=30) compared with healthy subjects matched by sex and age (N=28) (P<0.001). Furthermore, in a test population of 106 asymptomatic subjects, we showed that sTWEAK concentrations negatively correlated with the carotid intima-media thickness (r=–0.4; P<0.001), an index of subclinical atherosclerosis.

Conclusions— These results suggest that sTWEAK could be a potential biomarker of atherosclerosis.

Using a proteomic approach, we have identified sTWEAK as a protein released in lesser amounts by atherosclerotic plaques than healthy arteries. Reduced sTWEAK plasma levels were detected in carotid atherosclerotic patients than in healthy subjects. sTWEAK levels negatively correlated with carotid IMT index. sTWEAK is a potential biomarker of atherosclerosis.

Key Words: atherosclerosis • carotid arteries • plasma