Decoding Monocyte Metabolism in Myocardial Infarction: A Time-Sensitive Approach to Limiting Heart Failure

ongoing

Cardiovascular diseases (CVD), particularly myocardial infarction (MI), are partly driven by chronic inflammation, in which myeloid cells, such as monocytes and macrophages, play a central role. This project aims to elucidate the metabolic mechanisms regulating monocyte function and their impact on post-MI recovery. Emerging evidence suggests that the metabolic state of myeloid progenitor cells and their descendants critically influences their pro- or anti-inflammatory functions. While glycolysis dominates early after MI, fatty acid oxidation takes over later stages, indicating that metabolic reprogramming is essential for monocyte and macrophage function. In this project, we will investigate the metabolic signatures of monocytes at different time points post-MI using a preclinical mouse model and the human HIBISCUS STEMI cohort. We aim to identify key metabolic pathways that can be targeted to modulate inflammation by employing single-cell RNA sequencing and single-cell metabolic assays. In mouse models, we will further test the effects of transiently inhibiting glycolysis or fatty acid oxidation in monocytes, using genetically modified mice, to determine whether this approach improves cardiac function and limits heart failure. Additionally, the fellowship will provide essential soft skills training in project management, mentoring, and grant writing, which are crucial for my transition to an independent research position. These skills will enhance my leadership abilities and prepare me for future academic and industrial opportunities. This research will provide new insights into the role of metabolism in myelopoiesis and inflammation and could lead to novel therapeutic strategies to improve outcomes in CVD patients.