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A causal role for remnant cholesterol in cardiovascular disease revealed.

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

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Nile Red Quantifier: a novel and quantitative tool to study lipid accumulation in patient-derived circulating monocytes using confocal microscopy.

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

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Cell paper published by the Radboud and Cluj-Napoca groups on the cholesterol synthesis pathway,

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

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Review paper on immune checkpoint proteins that orchestrate the chronic inflammation underlying atherosclerosis

  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

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Grant application OPERATION funded by European Research Area Network on Cardiovascular Diseases (ERA-CVD)

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.

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Innovative TRAF-STOP Treatment Reduces the Progression of Established Atherosclerosis and Induces a Stable Plaque Phenotype

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

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Remnant cholesterol elicits arterial wall inflammation

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,

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86th European Atherosclerosis Society meeting @ Lisbon, Portugal

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

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Lipid lowering with PCSK9 reduces the pro-inflammatory phenotype of monocytes

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

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Two REPROGRAM publications in Cell press!

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

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This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.