Welcome to the Horizon 2020 atherosclerosis research program website
In the first 6–9 months following an acute coronary syndrome (ACS), patients face a disproportionally increased risk of reinfarction. Following an ACS in patients, studies have substantiated that 18F-fluordeoxyglucose (18F-FDG) uptake in bone-marrow and spleen is increased, visualized with positron emission tomography/ computed tomography (PET/CT). This increased uptake coincides with increased inflammatory parameters in plasma
The groups of Prof. Stroes (Amsterdam) and Prof. Nahrendorf (Boston) reviewed recent advances in the connection between hematopoiesis and atherogenesis. Atherogenesis is the result of a complex interplay between lipids and innate immune cells, which are descendants of upstream progenitors residing in hematopoietic organs. The relevance of a neural–hematopoietic axis was recently supported by the demonstration of
The group from Radboud UMC (Prof. N. Riksen, Prof. M. Netea) co-authored a paper published in Cell earlier this year (11 January 2018) in which work from the REPROGRAM project is mentioned. Today, in Western societies, over 80% of deaths are due to non-communicable diseases including those associated with aging and diseases caused or influenced by the consumption of
The interaction between the different immune cells, and the (subsequent) secretion of immune-regulatory and activating cytokines and chemokines determines the progression of atherosclerosis. Key players in modulating these complex immune interactions and responses are the group of co-stimulatory molecules. The group of Prof. Lutgens (LMU) et al found that inhibition of the co-stimulatory molecules CD40L and
REPROGRAM researchers of the Academic Medical Center (AMC) teamed up with researchers from Copenhagen, Denmark (REGIONH) to study the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Although the population with FD is an extreme model, elevated levels of (nonfasting) remnant cholesterol are present in 38% of men and
In a collaborative effort of the teams of Academic Medical Center and Servier a novel tool to study lipid accumulation has been developed. The inflammatory profile of circulating monocytes is an important biomarker for atherosclerotic plaque vulnerability. Recent research revealed that peripheral lipid uptake by monocytes alters their phenotype toward an inflammatory state and this
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
This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.