Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Abstract

Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.