Project: “The Role of the Pentose Phosphate Pathway on Myeloid Cell Activation and Atherosclerosis”

Acronym MyPenPath (Reference Number: JTC-2019_024)
Duration 01/05/2020 - 30/04/2023
Project Topic Atherosclerosis is the main cause of myocardial infarction and stroke, contributing to the global burden of cardiovascular diseases (CVD). Immune cell dysregulation and chronic inflammation are major causes of atherosclerotic plaque development. Importantly, myeloid cell activation in CVD is paralleled by an increase in glucose utilization. The Metabolic Syndrome (MetS) is hallmarked by chronic inflammation and the dysfunction of key processes that regulate glucose metabolism, escalating the risk of atherosclerosis. Thus, myeloid cell metabolic rewiring could have major implication in MetS, characterized by a gender-dependent nutrient overload and a dysregulated metabolic state, associated to insulin resistance and type 2 diabetes. We hypothesize that metabolic dysfunction in atherosclerosis reprograms glucose utilization in immune cells, leading to their expansion and activation in the plaque. This consortium associates interdisciplinary and key expertise to investigate the contribution of glucose metabolism, and in particular the balance between glycolysis and the pentose phosphate pathway (PPP), in immune cell functions during atherosclerosis. We will define the contribution of glycolysis and the PPP to immune cell migration, proliferation and activation in atherosclerosis using mouse genetic models and pharmacological inhibitors. Moreover, in a translational approach, our consortium will bring together human cohorts and expertise to delineate the impact of metabolic dysfunction on inflammation and CVD development in the clinical context.
Network ERA-CVD
Call ERA-CVD Joint Transnational Call 2019

Project partner

Number Name Role Country
1 INSERM Coordinator France
2 University Hospital Aachen Partner Germany
3 Medical University of Vienna Partner Austria
4 Amsterdam UMC Partner Netherlands