Impact of Heterogeneous Macrophage Origins on Ischaemic and Non-Ischaemic Cardiac Lesions (B08 (P08))

• Subject Area: Cell Biology ; Cardiology, Angiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

We will elucidate the roles of Hexb, a common injury response gene identified in our studies in the first funding period. Hexb is an enzyme that cleaves glycolipids and glycoproteins inside and outside of cells. Macrophages are a dominant source of Hexb in mouse and human hearts, and Hexb expression surges in response to ischaemic and non-ischaemic cardiac injury. We expect that a cardioprotective effect of Hexb on heterocellular remodelling involves supporting heterophagy, extracellular matrix organisation, and signal transduction. We will use transgenic mouse models to identify triggers of injury-related Hexb expression in cardiac macrophages, and to delete Hexb expression specifically in macrophages. Combining cardiac function testing, lipidome and proteome analyses, microscopy, and heterocellular gene expression profiling we will inform subsequent mechanistic studies, including in vitro co-culture experiments and in vivo enzymatic replacement or pharmacological chaperone treatment. In the long run, we plan to channel functional insight regarding cardiac macrophage injury response genes and their interactive effects on lesion formation into translational work involving large animals, human tissue samples, and patient cohorts.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professor Dr. Ingo Hilgendorf