FOR 6051:  The Interstitium – a Key Determinant of Cardiac Function

• Subject Area: Medicine ; Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564978926

Cardiac myocytes (CM) are the archetypic cell population of the heart, and they drive electro-mechanical function. Accordingly, CM have formed a focus of heart research. However, while CM make up around two-thirds of cardiac tissue by volume, they are dwarfed in terms of cell numbers by non-myocytes (NM), including fibroblasts, immune cells, or endothelial cells. It is becoming increasingly clear that NM, and the extracellular matrix (ECM), are crucial determinants of cardiac structure and function in health, ageing, and disease. NM are found in three tissue sub-types of the heart: the coronary vascular & lymphatic system, the intracardiac nervous system, and the interstitium. The interstitium (literally 'that what stands in-between') provides structural stability to the heart, integrates CM with the intracardiac vascular and nervous systems, and generates a signalling microenvironment that is crucial for homeostasis of individual cells and the heart as a whole. Given this importance, it is surprising how little is known about the interstitium, its (auto-)regulation, and its functional relevance for the heart. Our highly interdisciplinary FOR plans to investigate the role of the interstitium for cardiac electrical and mechanical activity by characterizing interstitial NM, ECM, and their interactions with each other and with CM, with the long-term vision of ultimately laying a new, interstitium-aware foundation for steering cardiac structure and function for patient benefit. We intend to do this by: 1) analyzing interstitial organization and mechanisms of remodeling - from nano-domain interactions between CM and interstitial NM cell-cell contacts that are relevant for ECM (re-)organization and maintenance, to the electrical and mechanical consequences of interstitial plasticity at cell, organ and organism levels; 2) comparatively characterizing roles of the cardiac interstitium in healthy hearts, during ageing, and in pathologies leading to fibrosis, including focal replacement fibrosis (e.g. after cardiac lesions due to myocardial infarction) and more diffuse, reactive interstitial fibrosis (e.g. in mechanical overload); 3) identifying mechanisms that determine the severity of pathological outcomes of interstitial remodeling, exploring biophysical and biochemical interactions of CM, immune and connective tissue cells, and ECM; 4) developing novel approaches to direct interventions not merely to an organ, a cell type, or ‘the’ ECM in general, but to defined sub-regions of the cardiac interstitium, such as specifically to ECM in infarcted myocardium.

• DFG Programme: Research Units

Projects

• Coordination Funds (Applicant Kohl, Peter )
• P1: Principal Categories of Interstitial Non-Myocyte Electrophysiological Effects on Cardiac Action Potential Propagation In Vitro and In Silico (Applicants Kohl, Peter ;  Loewe, Axel )
• P2: ECM Deposition at the Fibroblast–Cardiomyocyte Nano-Interface (Applicants Lehnart, Stephan E. ;  Rog-Zielinska, Ph.D., Eva )
• P3: Effects of Cardiac Electro-Mechanical Activity on Interstitial Non-Myocytes (Applicants Schneider-Warme, Franziska ;  Streckfuß-Bömeke, Katrin )
• P4: Age-Associated Changes in Immune Cell Contributions to Early Interstitial Remodelling (Applicants Grune, Jana ;  Lenz, Christof )
• P5: Impact of Interstitial Remodelling on the Rate Dependence of Cardiac Conduction (Applicants Huisken, Jan ;  Zgierski-Johnston, Callum Michael )
• P6: Stretch-Activated Ion Channels in Non-Myocytes Linking Cardiac Mechanics, Interstitial Remodelling, and Arrhythmogenesis (Applicants Lother, Achim ;  Peyronnet, Remi )
• P7: Differential silencing of key collagen maturation steps as a way to control diffuse and focal interstitial fibrosis of the heart (Applicants Hilgendorf, Ingo ;  Lindner, Diana )
• Targeting the Interstitium to Alter Fibrotic Remodelling in the Heart in vivo (Applicants Briquez, Ph.D., Priscilla ;  Kessler, Thorsten )

• Spokesperson: Professor Dr. Peter Kohl