Omics-based Approach Towards Macrophages: New Perspectives of Biology and Function in the Normal and Diseased Heart

Macrophages play a crucial role not only in maintaining homeostasis but also in initiating inflammatory responses to various forms of stress or injury, thereby contributing to tissue damage while concurrently promoting recovery. Furthermore, the diversity of macrophage subtypes, their spatial distribution, and distinct cellular functions are closely linked to the pathogenesis and severity of cardiovascular diseases such as myocardial infarction, atherosclerosis, heart failure, and myocarditis. This association underscores the importance of investigating macrophage heterogeneity in different pathological contexts. Recent advances in multi-omics technologies-including single-cell RNA sequencing, spatial transcriptomics, and metabolomics-have elucidated the heterogeneity of macrophages, their intercellular interactions, underlying functional mechanisms, and spatial organization. In this review, we systematically summarize the diverse phenotypes and functional plasticity of macrophages in the regulation of cardiovascular diseases, with particular emphasis on the novel insights afforded by multi-omics approaches. We focus on the characteristics of macrophages in both physiological and pathological states, thereby providing reference points for clinical macrophage-targeted strategies and their translational significance.