Macrophages in vascular inflammation – From atherosclerosis to vasculitis

Abstract

The spectrum of vascular inflammatory disease ranges from atherosclerosis and hypertension, widespread conditions affecting large proportions of the population, to the vasculitides, rare syndromes leading to fast and irreversible organ failure. Atherosclerosis progresses over decades, inevitably proceeding through multiple phases of disease and causes its major complications when the vessel wall lesion ruptures, giving rise to lumen-occlusive atherothrombosis. Vasculitides of medium and large arteries progress rapidly, causing tissue ischemia through lumen-occlusive intimal hyperplasia. In both disease entities, macrophages play a decisive role in pathogenesis, but function in the context of other immune cells that direct their differentiation and their functional commitments. In atherosclerosis, macrophages are involved in the removal of lipids and tissue debris and make a critical contribution to tissue damage and wall remodeling. In several of the vasculitides, macrophages contribute to granuloma formation, a microstructural platform optimizing macrophage–T-cell interactions, antigen containment and inflammatory amplification. By virtue of their versatility and plasticity, macrophages are able to promote a series of pathogenic functions, ranging from the release of cytokines and enzymes, the production of reactive oxygen species, presentation of antigen and secretion of tissue remodeling factors. However, as short-lived cells that lack memory, macrophages are also amendable to reprogramming, making them promising targets for anti-inflammatory interventions.

• Atherosclerosis
• macrophage
• vascular inflammation
• vasculitis

Acknowledgements

Research studies informing this work received critical support from the Govenar Discovery Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Declaration of interest

No conflict of interest is declared by the authors. This work was supported by the National Institutes of Health (R01 AR042547, R01 HL117913, R01 AI044142, R01 AI108906 and P01 HL058000 to CMW and R01 AI108891 and R01 AG045779 to JJG).