Welcome to the Horizon 2020 atherosclerosis research program website
Bekkering et al (2018) published their groundbreaking results on the cholesterol synthesis pathway, and in particular the intermediate mevalonate. This pathway is essential for inducing trained innate immunity, the key-concept of REPROGRAM. Highlights Induction of trained immunity by beta-glucan depends on intracellular mevalonate Mevalonate induces trained immunity in human monocytes Mevalonate-induced training is mediated through increased function of
Interactions between different immune cells result in the secretion of inflammatory mediators, such as cytokines and chemokines, and fuel atherogenesis. Immune checkpoint proteins have a critical role in facilitating immune cell interactions and play an essential role in the development of atherosclerosis. Although the therapeutic potential of these molecules is wellrecognized in clinical oncology, the use of immune
Prof. Erik Stroes (AMC, Amsterdam) and Prof. Alberico Catalano (UMIL, Italy) have teamed up with Prof. Wolfgang Koenig (TUM, Munich) and prepared a successful transnational ERA-CVD research application entitled OPERATION. The OPERATION project aims to combine state-of-the-art genome-scale metabolic modelling on plasma monocytes with plasma proteomics to select a biomarker pattern correlating with arterial wall inflammation.
In this paper the LMU (Munich) and AMC (Amsterdam) groups show that blocking CD40-TRAF6 interactions by Small Molecule Inhibitors (TRAF-STOP) treatment strongly reduces atherosclerosis by preventing activation of classical monocytes, leukocyte recruitment, and macrophage activation and migration in the arterial wall. TRAF-STOPs can overcome the current limitations of long-term CD40 inhibition in atherosclerosis and have the potential to become a
The groups of AMC (the Netherlands) and REGIONH (Denmark) collaborated on elucidating the mechanisms by which remnant cholesterol particles may induce inflammatory changes. Remnant cholesterol can be readily taken up by plaque macrophages without previous oxidation of the particle, thereby promoting arterial inflammation. This reaction propagates continued influx of circulating immune cells, predominantly monocytes, into atherosclerotic lesions in both experimental models8 and patients,
With many world-leading experts already confirmed in the scientific programme, EAS 2018 Lisbon (5-8 May) is the place to come for a bench-to-bedside overview of the latest current research in the field. Be inspired by the award-winning Anitschkow Lecture, by outstanding Keynote lectures, by state-of-the-art Plenary sessions, and focussed Workshops and Advanced Clinical Seminars. EAS
In the high impact European Heart Journal, The AMC group (Bernelot Moens et al) published a European Heart Journal paper on the impact of LDL cholesterol lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia not using statins due to statin-associated muscle symptoms.. This open-access article can be found here (doi:10.1093/eurheartj/ehx002). The group shows that lipid lowering
The RadboudUMC group led by Prof. Niels Riksen and Prof. Mihai Netea very recently published cutting edge results in Cell press about influencing our immune system by utilizing the “Trained Immunity” concept, key to the REPROGRAM project. Metabolic induction or trained immunity involves mevalonate pathway, Siroon Bekkering et al., Cell, January 11, 2018 Cholesterol inhibitor
In the high impact European Heart Journal, the REPROGRAM consortium published an invited review of the REPROGRAM concepts and approaches. This open-access article can be found here (doi:10.1093/eurheartj/ehx581) Main message: Chronic inflammatory diseases are the most common diseases of ageing and represent one of our major health threats. These include. most forms of cardiovascular diseases,
Agnieszka Pajak, a REPROGRAM-dedicated PhD-student working at the University Hospital Zurich (Switzerland) on Trained Immunity in rheumatoid arthritis was invited to give a talk at the Annual European Congress of Rheumatology (European League Against Rheumatism, EULAR). The following EULAR congress is planned in Amsterdam (the Netherlands) from 13 till 16 June 2018.
This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.