Targeting monocyte heterogeneity in aortic aneurysms: immunomodulatory strategies and therapeutic opportunities

Aortic aneurysms (AA) remain life-threatening vascular disorders characterized by progressive dilatation and risk of rupture. Despite advances in surgical and endovascular repair, pharmacological therapies to prevent aneurysm progression are lacking. Increasing evidence implicates chronic vascular inflammation and monocyte-derived macrophages in the pathogenesis of AA via matrix degradation, smooth muscle cell apoptosis, and neovascularization. Monocytes, traditionally classified as classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) subsets, exhibit diverse functions in immune surveillance, cytokine production, and tissue remodeling. This review addresses the mechanistic roles of monocyte subsets in AA progression, evaluates emerging immunomodulatory strategies including CCR2 and TREM-1 inhibition, metabolic reprogramming, nanoparticle delivery, and cell-based therapies, and explores their integration with current surgical practices. Identification of circulating monocyte phenotypes may serve as promising biomarkers for patient stratification, monitoring, and therapeutic guidance. Advances in single-cell transcriptomics may reveal dynamic monocyte-macrophage phenotypes in aneurysm tissue. Current data hold promises for providing new perspectives on therapeutic strategies targeting monocytes. However, data are largely derived from preclinical studies. Detailed clinical studies are needed. Furthermore, translating these insights into clinical practice requires multidisciplinary collaboration among experts in immunology, vascular surgery, imaging, and systems biology.