P322	ED-A, an endogenous ligand for toll like receptor -4, is not associated with the extent or progression of atherosclerotic disease or atherosclerotic plaque phenotype.
1K.van Keulen, 2A.Schoneveld, 2F.Moll, 3Y.de Graaf, 1D.de Kleijn, 1G.Pasterkamp
1Experimental Cardiology/UMCU, Utrecht, NL; 3Utrecht, NL & 2Utrecht, NL.

Background. Extra Domain A (ED-A), an alternative spliced form of fibronectin is a ligand for the Toll Like Receptor 4 (TLR4) and expressed in mouse and human atherosclerotic tissues. Recently it has been demonstrated that ED-A enhances atherosclerotic lesion formation in mice. We hypothesized that ED-A is a marker of atherosclerotic disease and associated with a vulnerable plaque phenotype. Methods. ED-A levels were assessed in :A- plasma obtained from 73 patients suffering from clinically evident atherosclerotic disease versus 68 controls matched for risk factors. B- 196 carotid endarterectomy specimen to relate plaque phenotype with local ED-A levels. All plaques were stained for the presence of macrophages, smooth muscle cells, collagen and fat and scored semiquantitatively as no/minor/moderate/heavy staining. C- plasma and plaque samples of 43 patients included in a longitudinal study undergoing carotid endarteretomy who developed a secondary major adverse cardiovascular event (MACE) during two years follow up versus 153 patients who remained healthy during follow up. Results. Ad A- ED-A levels did not differ between atherosclerotic versus non atherosclerotic patients (7.1+/-0.69 versus 6.9+/0.51, respectively, p=0.20). In this population carotid intima media thickness did not differ among ED-A quartiles (p>0.50). Ad B- Symptomatic patients showed lower ED-A plaque values compared with asymptomatic patients (17.1+/-1.6 versus 27.0+/-3.8, p=0.004). Atheromatous plaques tended to show lower ED-A values compared with fibrous and fibro-atheromatous plaques but this was not significant (15.26+/-3.11, 20.5+/-2.6, 20.2+/-2.1, respectively, p>0.10). ED-A levels were not related with macrophage, smooth muscle cell or collagen staining. In this population CRP levels did not correlate with plasma ED-A levels. Ad C- No difference was observed in ED-A levels between patients that reached an endpoint (MACE) compared with patients who did not (plaque: 19.53+/-3.4 versus 19.74+/-2.9; plasma:10.9 +/- 1.9 versus 11.9 +/-2.6, all p>0.50). Conclusion: The TLR-4 ligand ED-A is not a marker for atherosclerotic disease or predictive for cardiovascular events. In addition, ED-A is not related with an inflammatory, vulnerable plaque phenotype.

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