The Inflammatory-Fibrosis Axis in Ischemic Heart Failure: translating mechanisms into new diagnostics and therapeutics

• Florian LEUSCHNER, Heidelberg University Hospital (Germany)

• Robert GROPLER, Washington University School of Medicine (USA)

Inflammation and fibrosis represent cardinal hallmarks of myocardial remodeling and heart failure progression. Despite a wealth of data documenting robust clinical associations, proof of concept causation, and putative disease mechanisms, it has remained challenging to effectively target inflammation and fibrosis in the human heart. Until recently, the exact cell types that mediate these important pathological processes were not well defined. Members of this network have identified an inflammatory-fibrosis axis comprised of chemokine C–C motif receptor-2 (CCR2) expressing monocytes and macrophages and activated fibroblasts expressing fibroblast activation protein (FAP) that are essential for the development and progression of heart failure in animal models. The overarching goals of this network are: 1) Establish the molecular basis by which myocardial inflammation orchestrates key elements of adverse left ventricular (LV) remodeling including myocardial fibrosis, translate molecular imaging strategies that will visualize mechanistic elements relevant in both pre-clinical disease models and humans, and develop therapeutic approaches that limit and/or reverse pathological cardiac fibrosis; 2) Accelerate scientific breakthroughs and innovation through team science engendered by the network and; 3) Generate multi-disciplinary training programs in cardioimmunology to train the next generation of scientists We believe that these mechanistic and translational studies will identify new opportunities to improve the longevity and health of patients with LV remodeling and heart failure. Moreover, the network will train a multi-disciplinary workforce to advance and apply this science and lay the foundation for future training programs in cardio-immunology. These outcomes will advance the mission of the Leducq Foundation to “improve human health through international efforts to combat cardiovascular disease and stroke.”