A008 Presence of tissue factor and other components of atherosclerosis in human aortic valve stenosis

BackgroundIt is now generally accepted that calcific aortic valve disease is 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 atherosclerotic 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.MethodsCalcified aortic valves (n=52) were obtained from patients undergoing aortic valve replacement. Leaflet structure, cellular and lipid infiltration and expression of TF, its inhibitors, VEGF and other components of atherosclerosis were evaluated by histological and immunohistochemical staining. TF, TFPI, osteopontin, MMP- 9, TIMP-1 and VEGF antigen were measured by ELISA and TF and alkaline phosphatase activity were determined using chromogenic assays. Finally, we performed semi-quantification of TF transcripts by RT- PCR and further analyzed protein expression by Western blot.ResultsHistological and immunohistochemical staining of the valve leaflets revealed neovascularisation at the centre of the lesions, overall macrophage and myofibroblast infiltration and the abundant presence of MMP-9. On the other hand, TF and TFPI 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 and activity were found to be higher in calcified regions of the valve leaflets (733.29±70.49pg/mgvs 429.40±73.17pg/mg and 144.75±14.65pg/mgvs 40.15±6.19pg/mg respectively (p<0.0001)). Similar results were found for osteopontin, MMP-9, TIMP-1 and VEGF. In contrast, TFPI antigen was found to be much lower in these calcified regions (722.54±153.92pg/mgvs 2459.28±285.36pg/mg (p<0.0001)).ConclusionThese results demonstrate that aortic valve lesions display several characteristics of atherosclerosis, including TF expression. In addition, we showed that TF is colocalized with calcification and lipid deposition. Further studies are now set up to evaluate the role of TF in aortic valve disease and its association with other components of the atherosclerotic process

Une stèle anthropomorphe néolithique à Villeneuve (Alpes-de-Haute-Provence)

Corseaux S., Courtin Jean, D'Anna A., Mosset Christian. Une stèle anthropomorphe néolithique à Villeneuve (Alpes-de-Haute-Provence). In: Bulletin de la Société préhistorique française, tome 81, n°4, 1984. pp. 113-116

The mechanisms of coronary restenosis: insights from experimental models

Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, ‘in-stent’ stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis