CLIPS-Prevention of serious vascular events by aspirin among patients with Periperal Arterial Disease:
published in J Intern Med 2007; 261: 276-284
European Data Bank on PAD patients: Concluded 3200 European PAD patients enrolled
Project by M. Catalano.
This is a co-operative project involving an extensive and proven European Network. The project concerns patients with Peripheral Vascular Disease (PAD) of the lower limbs, with no distinction between stages. It calls for the enrolment of 3000 patients, who will be investigated by means of a questionnaire and pre-established examinations. It has been the preliminary study to buit up the European Biobank. The study has aroused interest on a preliminary basis on the part of the European Science Foundation, which sponsored an Exploratory Meeting of the Centres in Milan. The following European countries will take part in the study: Italy, France, Germany, Switzerland, Austria, Greece, Belgium, the UK, Sweden, Slovenia, Rumania, Poland ,Spain and Argentina (in the order in which they joined). As of today, the study has organised its own structure, the questionnaire, the IT system and the statistical and epidemiological consulting.
Thrombin generation assessment in patients with atherothrombosis – Concluded
Project by G.T.Gerotziafas, E. Verdy, I.Elalamy, M. M. Samama – University of Paris (F)
Atherothrombosis is characterised by multifocal, disseminated and progressive atheromatic lesions of arterial wall, platelet activation and activation of blood coagulation leading to thrombus formation. Thrombin generation assay was developed several years ago to mimic physiological coagulation mechanisms but it had important limitations. Thrombogram-Thrombinoscope assay using a fluorogenic substrate, allows obtaining thrombin generation curves in non-defibrinated platelet rich plasma (PRP) in a fully automated manner. Chronic elevation of indicators of coagulation activation has been found in patients with peripheral arterial disease, but a role of coagulation activation as a potential risk factor for PAD has not been investigated. Since an increasing body of evidence shows that Thrombogram-Thrombinoscope assay may be a useful tool in the diagnosis of several hypercoagulable states, the purpose of the present project is to investigate the parameters of thrombin generation in patients with PAD. This project could have implications for risk assessment and genetic screening of patients prone to PAD.
Immunologic markers associated with PAD
Project by M. Catalano and M. Clerici, University of Milan (I)
Inflammation is central at all stages of atherosclerosis and adaptive immunity, in particular T cells, is highly involved in atherogenesis. It is also well known that different subsets of T cells can drive or dampen inflammatory processes. Inflammation and immunity are implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infilration into the subendothelium. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways. There is growing evidence regarding the importance of inflammation in the pathogenesis of peripheral arterial disease (PAD). Recently there has been an increasing interest in the role of helper T (Th) cells in PAD. The Th cells act with the macrophages and the dendritic cells via the various cytokines in bringing about a variety of changes thus leading to the progression of PAD. Atherosclerotic lesions have been seen to have increased expression of type 1 helper T (TH1) cells together with increased levels of the Th1 related cytokines. It is mainly the cytokines involved with Th1 functioning that seem to show a prominent effect, with the whole process centred around interferon gamma, making it seem like every pathway and the cytokines involved lead to a final common pathway of interferon gamma secretion; the increase or decrease of which dictates the progression of PAD and its final manifestation as the clinical syndromes. The aim of the present project is to shed more light on the potential role of monocyte/lymphocyte recruitment in PAD by immunophenotyping of peripheral leukocytes.