Tissue-Resident Macrophages in Cardiovascular Diseases: Heterogeneity and Therapeutic Potential.

Tissue-resident macrophages (TRMs) play a crucial role in maintaining tissue homeostasis and regulating immune responses. In recent years, an increasing number of studies have highlighted their central role in cardiovascular diseases. This review provides a comprehensive overview of TRMs, with a particular emphasis on cardiac resident macrophages (CRMs), discussing their origin, heterogeneity, and functions in various cardiovascular diseases. We conduct an in-depth analysis of macrophage subpopulations based on C-C Chemokine Receptor Type 2 (CCR2) receptor expression, elucidating the role of CCR2 macrophages in promoting fibrosis and cardiac remodeling, while highlighting the protective functions of CCR2 macrophages in suppressing inflammation and promoting tissue repair. In atherosclerosis, we focus on the role of metabolic reprogramming in regulating macrophage polarization, revealing how metabolic pathways influence the balance between pro-inflammatory M1 and anti-inflammatory M2 macrophages, thereby affecting plaque stability and disease progression. By summarizing the roles of these macrophage subpopulations in myocardial infarction, heart failure, and other diseases, we propose potential therapeutic strategies aimed at modulating different macrophage subtypes. These include targeting the CCR2 signaling pathway to mitigate inflammation and fibrosis, and metabolic reprogramming to restore the balance between M1 and M2 macrophages. Finally, we highlight the need for future research to focus on the functional diversity and molecular mechanisms of human TRMs to develop novel immunotherapeutic strategies and improve the prognosis of cardiovascular diseases.