Project: Macrophage heterogeneity in human and murine atherosclerosis: a therapeutic opportunity?

Acronym	AtheroMacHete (Reference Number: 9. JTC-2017_63)
Project Topic	Atherosclerosis-related cardiovascular diseases are the most important causes of death worldwide. As the most abundant immune cell type in the plaque, macrophages play crucial roles in the pathogenesis throughout the disease course. Due to their versatile and plastic phenotype in response to locally-produced factors, and depending on differences in their ontogeny (monocyte-derived vs. tissue-resident), macrophages are very heterogeneous and can exert pro- as well as anti-atherogenic activity. As context and origin, and hence macrophage heterogeneity, are disease stage-dependent, this considerably complicates the design of effective macrophage-targeting therapies. Here, a complimentary team of experts in plaque pathophysiology (EB), macrophage systems biology (JS), macrophage differentiation (MS) and cardiovascular medicine (PA) joins forces to tackle this major challenge. We will provide a detailed transcriptional, ontogenic, contextual and functional macrophage map for several disease stages. These unprecedented new insights into atherosclerotic macrophage heterogeneity in human and mouse will allow identification of gene programs and regulatory cues driving critical functions of plaque macrophages. Finally, through a network-guided systems medicine approach we will identify effective compounds based on known interactions between existing FDA approved drugs and our identified molecular networks, validate them in in vitro high throughput screenings, in vivo mouse models, ex vivo human plaques and provide proof-of-concept for clinical applications.
Network	ERA-CVD
Call	Joint Transnational Call for Proposals 2017: Mechanisms of early atherosclerosis and/or plaque instability in Coronary Artery Disease

Project partner

Number	Name	Role	Country
1	Maastricht University	Coordinator	Netherlands
2	LIMES Institute, University of Bonn		Germany
3	Centre d’Immunologie de Marseille-Luminy		France
4	Research Institute of Internal Medicine, University of Oslo		Norway