Project: Elucidate monocyte phenotype to predict arterial wall inflammation

Acronym	OPERATION (Reference Number: 4. JTC-2017_45)
Project Topic	Up to 70% of cardiovascular (CV) events are not prevented despite optimal lipid-lowering therapies. In search for additional strategies, immune–cell driven inflammation of the arterial wall has been recognized as a key player contributing to atherosclerotic plaque initiation and eventually destabilization. Biomarkers capturing inflammatory activity of arterial plaques in patients have been put forward as a promising tool in CV-risk assessment. To date, traditional plasma biomarkers of inflammation have however failed to predict arterial wall inflammation. In view of the cumulative evidence supporting a role of the innate immune system in atherogenesis, there has been increasing interest in the determination of monocyte function and accompanying plasma metabolites as markers for CV-risk. Here, the phenotype of circulating monocytes is believed to serve both as an indicator of disease burden as well as prognostic marker in CV-prevention. In this project called OPERATION, we propose 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. Subsequently, advanced machine-learning will be applied to optimize a biomarker pattern predicting CV-risk, which will be validated in primary and secondary prevention cohorts available to this consortium. The end-result is the delivery of a clinically relevant and industrially usable integrated inflammatory plasma biomarker pattern which will enable us to accurately identify patients at residual inflammatory CV-risk.
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	Academic Medical Center	Coordinator	Netherlands
2	IRCCS MultiMedica - MultiMedica SPA	Partner	Italy
3	Technische Universitat Munchen	Partner	Germany