Identification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis.
OBJECTIVE
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.


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.
Blanco-Colio
Luis M
LM
Vascular Research Laboratory, Fundación Jiménez Díaz, Autonoma University, 28040, Madrid, Spain. lblanco@fjd.es
Martín-Ventura
Jose L
JL
Muñóz-García
Begoña
B
Orbe
Josune
J
Páramo
Jose A
JA
Michel
Jean-Baptiste
JB
Ortiz
Alberto
A
Meilhac
Olivier
O
Egido
Jesús
J
D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism; D016893:Carotid Stenosis / Q000378:metabolism; D000074049:Cytokine TWEAK; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D048069:Tumor Necrosis Factors / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism
D015415:Biomarkers; D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors