Abstract
Background
Extra domain A (EDA), splice-variant of fibronectin, is a Toll-like receptor 4 (Tlr4)
ligand. Recently, EDA has been demonstrated to enhance atherogenesis in mice but human
data on the role of EDA in atherosclerotic disease are lacking. We hypothesized that
EDA is associated with unstable plaque phenotypes and that plasma EDA could serve
as biomarker for atherosclerosis.
Methods
EDA levels were assessed in carotid endarterectomy specimen (206 patients) and related
with plaque phenotype. In a second patient cohort, systemic EDA levels in atherosclerotic
patients (73 patients) were compared to risk-factor matched controls (68 patients).
Results
EDA plaque levels were associated with characteristics of stable plaques; more smooth
muscle cells (P = 0.003), more collagen (P = 0.071) and less fat (P = 0.023). Concomitantly, asymptomatic patients showed higher EDA values in the plaque
compared to symptomatic patients (P = 0.004). EDA plasma levels did not differ between atherosclerotic patients versus controls
(P = 0.134).
Conclusion
EDA plaque levels are higher in asymptomatic patients and are associated with a stable
plaque phenotype. EDA is not a plasma marker for atherosclerotic disease. These results
suggest that local presence of endogenous Tlr4 ligand EDA is not associated with in
an unstable plaque phenotype in humans.
Keywords
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Article info
Publication history
Published online: April 11, 2007
Accepted:
March 8,
2007
Received in revised form:
March 2,
2007
Received:
November 30,
2006
Identification
Copyright
© 2007 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.