Abstract 6146: Atherosclerotic-Like Processes in Human Aortic Valve Disease: Role of Tissue Factor and Other Components of Atherosclerosis
Background: Calcific aortic valve stenosis is considered to be an atherosclerotic-like process. Recent studies in an experimental model of aortic valve sclerosis demonstrated the presence of tissue factor (TF), the main contributor to plaque thrombogenicity, in diseased valve leaflets. We assessed the hypothesis that human aortic valve disease is an atherosclerotic-like process in which TF plays an important role and evaluated the valvular expression and localization of TF and other components of atherosclerosis.
Methods: Calcified aortic valves were obtained from 52 patients (age 70.1 ± 1.4 years; 31 men; 13 bicuspids; mean transvalvular gradient 54.6 ± 2.4 mmHg; mean valve orifice 0.74 ± 0.41 cm2) undergoing valve replacement. Leaflet structure, cellular and lipid infiltration, neovascularization and expression of TF, TF Pathway Inhibitor (TFPI), VEGF and other components of atherosclerosis were evaluated by immunohistochemical staining. TF and VEGF antigen were measured using ELISA kits or by Western blot. TF and alkaline phosphatase (ALP) activity were determined using chromogenic assays. Finally, we quantified TF and VEGF transcripts by real-time PCR.
Results: Immunohistochemical studies revealed neovascularisation at the centre of the aortic valve lesions and overall macrophage and myofibroblast infiltration. TF and TFPI expression were associated with calcification and extracellular lipid deposits in the fibrosa and the subendothelial layer of the aortic side of the leaflets. Correspondingly, TF antigen, activity and expression were found to be higher in calcified regions of the valve leaflets (733.29 ± 70.49 pg/mg vs 429.40 ± 73.17 pg/mg and 144.75 ± 14.65 pg/mg vs 40.15 ± 6.19 pg/mg respectively; p<0.0001). Similar results were found for VEGF. Additionally, both TF antigen and activity were significantly correlated with ALP activity (p<0.0001 and p<0.05 respectively).
Conclusion: Aortic leaflet TF expression is a new and important feature of aortic valve stenosis. TF colocalizes with calcification and is associated with ALP activity and hence may be involved in the atherosclerotic and mineralization process of aortic valves. Further studies are needed to evaluate the role of TF in aortic valve disease and lesion progression.