Abstract
Macrophages are a cell type that are known to play dynamic roles in acute and progressive pathology. They are highly attuned to their microenvironments throughout maturation, tailoring their functional responses according to the specific tissues in which they reside and their developmental origin. Cardiac macrophages (cMacs) have emerged as focal points of interest for their interactions with the unique electrical and mechanical stimuli of the heart, as well as for their role in maintaining cardiac homeostasis. Through an in-depth analysis of their origin, lineage, and functional significance, this review aims to shed light on cMacs' distinct contributions to both normal physiological maintenance as well as disease progression. Central to our discussion is the comparison of cMac characteristics between mouse and human models, highlighting current challenges and proposing novel experimental tools for deciphering cMac function within the intricate human cardiac microenvironments based on current murine studies. Our review offers valuable insights for identifying novel therapeutic targets and interventions tailored to the distinct roles of these immune cells in cardiovascular diseases (CVDs).