Category: Publications

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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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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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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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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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Invited review on the REPROGRAM project in European Heart Journal

  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,

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Cell Metabolism review: Importance of cellular metabolic rewiring during myeloid cell activation

Renewed interest in immune cell metabolism has led to the emergence of a research field aimed at studying the importance of metabolic processes for an effective immune response. In addition to the adaptive immune system, cells of the myeloid lineage have been shown to undergo robust metabolic changes upon activation. In the Cell Metabolism paper, published by

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Epigenetic remodeling and the use of ‘epigenetic drugs’ are a promising tool for future treatment of atherosclerosis.

Bonn University (Prof. Eike Latz) and Radboud University Medical Center Nijmegen (Prof. Niels Riksen and Dr. Siroon Bekkering) published a review in the journal Seminars on Immunology in which they discuss the concept of trained innate immunity in the context of a hyperlipidemic environment and atherosclerosis. According to this idea the epigenome of myeloid (progenitor) cells is presumably modified

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Scientific publication in European Heart Journal

Sophie J. Bernelot Moens, junior researcher in the group of Prof. Erik Stroes and Prof. Menno de Winther (Academic Medical Center) recently published her results in European Heart Journal on how PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies increase hepatic low-density lipoprotein receptor expression and show potent low-density lipoprotein

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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.