Macrophage-Mediated Mechanisms of Vascular Remodeling in Arteriovenous Malformations

Arteriovenous malformations (AVMs) are vascular malformations that can occur in virtually all tissues throughout the body, most commonly in the brain, lungs, and cutaneous tissue. AVM pathophysiology is dynamic and multifactorial with multiple contributing cell types and biological processes. Inflammation and perivascular accumulation of macrophages are well-recognized components of AVM pathophysiology that have been demonstrated for decades in both patient AVM tissue and animal models. Despite the clinical and preclinical data identifying a role for macrophages in AVM pathophysiology, it remains poorly understood how macrophages mechanistically contribute to AVM initiation and progression. Recent single-cell RNA sequencing studies leveraging clinical AVM samples are beginning to shed new light on macrophage diversity in AVM tissue and direct macrophage-mediated effects on endothelial cell signaling pathways. This review will focus on fundamental aspects of AVM pathophysiology, mechanisms of macrophage-mediated vascular remodeling in AVMs, and potential future research directions focused on macrophage-mediated mechanisms in AVM pathophysiology.