de Winther M.P.J.: Macrophage regulation in atherosclerosis

  • Aarts, Suzanne (Internal PhD candidate)
  • Baardman, Jeroen (Internal PhD candidate)
  • van den Berg, Susan (Internal PhD candidate)
  • Chen, Hung-Jen (Oliver) (Internal PhD candidate)
  • Ghiboub, Mohammed (Internal PhD candidate)
  • Kusters, Pascal (Internal PhD candidate)
  • Loring, Svenja (Internal PhD candidate)
  • Luque Martin, Rosario (Internal PhD candidate)
  • Neele, Annette (Internal PhD candidate)
  • Ruizendaal, Esmèe (Internal PhD candidate)
  • Schilderink, Ronald (Internal PhD candidate)
  • Smeets, Esther (Internal PhD candidate)
  • de Winther, Menno (Principal investigator)
  • Gijbels, Maria (Staff)
  • Van den Bossche, Jan (PostDoc)
  • van der Velden, Saskia (Other)
  • van der Vorst, Emiel (External PhD candidate)
  • Wolfs, Ine (External PhD candidate)

Project Details


In this program we are investigating the regulation of macrophages, as key immune cells shaping atherosclerotic plaque development and stability.
We are using a unique approach of cellular murine and human monocyte and macrophage tools combined with state-of-the-art mouse models and cells and tissue samples from cardiovascular disease patients to cover the complete axis from fundamental mechanistic work to applied translational studies.
We have three main interests. 

First, we are studying key cytokines and signaling pathways that regulate macrophage function, by the use of cell specific knockouts in atherosclerosis models. A key focus is on cytokine and lipid driven regulation of macrophage subtypes, such as described by the M1-M2 paradigm and we are investigating the effects of macrophage polarizing cytokines such as IL-10 and IFNgamma on atherosclerosis development and lipid metabolism. Our previous data has shown that type I interferons act pro-atherogenic and we are further studying underlying mechanisms. In the past we have also demonstrated a key role for NF-kB in regulating macrophage and endothelial responses in atherogenesis. On-going studies focus on these and other transcription factors that regulate macrophages.
Second, we are investigating the influence of the hyperlipidemic setting in which atherosclerosis develops and the role of cellular energy metabolism on the phenotype of atherosclerotic macrophages. This is combined with novel approaches to skew macrophages from a pro- to an anti-atherogenic phenotype.
Finally, we are investigating histone-modifying epigenetic mechanisms that control macrophages in inflammatory responses and atherosclerosis. We have identified enzymes that regulate histone modifications in macrophages in response to differentiation, activation, polarization or lipid loading and are using chemical and genetic tools to influence these enzymes to control and drive monocyte and macrophage responses to a beneficial phenotype.
With this knowledge novel therapeutic approaches and diagnostic tools may be initiated and better adapted to current treatments.
Effective start/end date1/10/2011 → …