Resident and Monocyte-Derived Macrophages in Cardiovascular Disease

Abstract

Macrophages are ubiquitous cells that reside in all major tissues. Counter to long-held beliefs, we now know that resident macrophages in many organs are seeded during embryonic development and self-renew independently from blood monocytes. Under inflammatory conditions, those tissue macrophages are joined and sometimes replaced by recruited monocyte-derived macrophages. Macrophage function in steady state and disease depends on not only their developmental origin but also the tissue environment. Here, we discuss the ontogeny, function, and interplay of tissue-resident and monocyte-derived macrophages in various organs contributing to the development and progression of cardiovascular disease.

Keywords: cardiovascular disease; hematopoietic system; inflammation; macrophage ontogeny; tissue-resident macrophages.

Figure 1. Macrophages in cardiovascular disease

During MI, atherosclerosis and stroke, monocytes are supplied by medullary and extramedullary hematopoiesis in bone marrow and spleen. Monocytes infiltrate diseased tissues, differentiate into macrophages and proliferate locally. In MI, resident cardiac macrophages are lost, while arterial macrophages in atherosclerosis persist. Cerebral microglia are activated after stroke and contribute to disease progression and healing. In obesity, macrophage accumulation in adipose tissue stems from local proliferation of resident and recruitment of monocyte-derived macrophages.

Figure 2. Macrophage mediators and crosstalk after myocardial infarction

TNF-α acts on cardiomyocytes and can induce hypertrophy and cell death. TGF-β induces conversion of fibroblasts to myofibroblasts that produce collagen necessary for scar formation. Proteolytic enzymes like matrix metalloproteinases (MMPs) contribute to tissue remodeling while VEGF acts on endothelial cells and stimulates angiogenesis.