Project Details
Projekt
P4: Age-Associated Changes in Immune Cell Contributions to Early Interstitial Remodelling
Applicants
Dr. Jana Grune; Dr. Christof Lenz
Subject Area
Cardiology, Angiology
Anatomy and Physiology
Cell Biology
Anatomy and Physiology
Cell Biology
Term
since 2026
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564978926
Myocardial infarction (MI) presents a significant global health burden, exacerbated by population ageing and the rising prevalence of risk factors such as obesity, hypertension, and diabetes. MI provokes extensive expansion of myocardial immune cells (IC), including neutrophils and monocytes, under inflammatory conditions. While ICs have been implicated in electrical conduction and cardiac tissue remodeling post-MI, mechanisms mediating communication between IC and major cardiac cell types, such as myocytes and fibroblasts, via the cardiac interstitium remain poorly understood. The increased risk of adverse MI outcomes, including arrhythmia, with age coincides with widespread immune system alterations, highlighting the need to elucidate IC contributions to MI pathophysiology and recovery. This project integrates three systems-level work packages (WP) to investigate the links between post-MI inflammation and interstitial remodeling. WP1 will leverage samples and data from the OPTICO-ACS II clinical trial to examine age-dependent dynamics of ICs after MI, correlating clinical outcomes with functional and proteomic analyses of IC subpopulations to associate immunological changes with arrhythmia risk. WP2 utilizes a mouse model of MI incorporating ageing to explore disease processes at molecular and structural levels, emphasizing the extracellular matrix (ECM) as the principal substrate for interstitial remodeling and extracellular vesicles (EV) as key mediators of cell communication. Mass spectrometry-based proteomics will profile ECM and EV contributions, complemented by spatial and cell type-specific proteome data, to identify age-related IC signaling signatures in interstitial remodeling post-MI. WP3 employs reductionist models: engineered heart muscle (EHM) will be exposed to IC secretomes to assess resultant structural and proteomic changes; additionally, an age-stratified mouse model of immune depletion and reconstitution will reveal the impact of immune ageing on post-MI outcomes by proteomic and functional analysis. In summary, the study will delineate the individual and synergistic roles of ageing and MI in neutrophil- and monocyte-driven cardiac interstitial remodeling, and define how protein-level IC signaling influences arrhythmia outcomes.
DFG Programme
Research Units
