Macrophages in Cardiovascular Fibrosis: Novel Subpopulations, Molecular Mechanisms, and Therapeutic Targets

Cardiovascular fibrosis is a common pathological process that contributes to the development and progression of various cardiovascular diseases. Despite being widely believed to be an irreversible and relentless process, preclinical models and clinical trials have shown that cardiovascular fibrosis is an extremely dynamic process. Additionally, as part of the innate immune system, macrophages are heterogeneous cells that are pivotal in tissue regeneration and fibrosis. They participate in fibroblast activation, extracellular matrix remodelling, and the regression of fibrosis. Although we have made some advances in understanding macrophages in cardiovascular fibrosis, a gap still remains between their identification and conversion into effective treatments. Moreover, the traditional M1-M2 paradigm faces many challenges because it does not sufficiently clarify macrophage diversity and their functions. Exploring novel macrophage-based therapies is urgent for cardiovascular fibrosis treatment. Single-cell techniques have shed light on identifying novel subpopulations that differ in function and molecular signature under steady-state and pathological conditions. In this review, we outline the developmental origins of macrophages, which underlie their functions; and recent technology development in the single-cell era. In addition, we describe the markers and mediators of the newly defined macrophage subpopulations and the molecular mechanisms involved to elucidate potential approaches for targeting macrophages in cardiovascular fibrosis. La fibrose cardiovasculaire est un processus pathologique courant qui contribue à l’apparition et à l’évolution de diverses maladies cardiovasculaires. S’il est généralement admis qu’il s’agit d’un processus irréversible et implacable, des modèles précliniques et des essais cliniques montrent que la fibrose cardiovasculaire est un processus extrêmement dynamique. En outre, les macrophages – qui font partie du système immunitaire inné – sont des cellules hétérogènes qui jouent un rôle essentiel dans la régénération et la fibrose tissulaires. Ils participent à l’activation des fibroblastes, au remodelage de la matrice extracellulaire et à la régression de la fibrose. Même si certains progrès ont été réalisés pour comprendre le rôle des macrophages dans la fibrose cardiovasculaire, des questions demeurent encore sans réponse pour ce qui est de bien les identifier et de savoir comment les convertir en traitements efficaces. Par ail