Unraveling the significance of innate inflammation in vascular disease

Abstract

Atheroma formation is initiated by the activation of endothelial and smooth muscle cells, as well as immune cells, including neutrophils, lymphocytes, monocytes, macrophages, and dendritic cells. Monocytes, macrophages, and neutrophils are the innate immune cells that provide a rapid initial line of defence against vascular disease. These cells have a short lifespan and cannot retain memories, making them potential therapeutic targets for the inflammatory process associated with atherosclerosis. In addition, macrophages comprise the majority of vessel wall infiltrates and are, therefore, implicated in all stages of atherosclerosis progression. Neutrophils are the most common type of leukocyte found in circulation, and their high levels of matrix-degrading protease explain their significance in fibrous cap destabilization. However, the activation of immune cells becomes more complex by various microenvironmental stimuli and cytokines, which ultimately transform immune cells into their pro-inflammatory state. Different types of macrophage subsets with distinct functions in inflammation, such as M1 macrophages, cause an increase in pro-inflammatory cytokines and produce reactive oxygen species and nitric oxide, further worsening the disease. This review aims to shed light on immune-mediated inflammation in cardiovascular disease by focusing on the role of macrophage subsets in vascular inflammation and plaque stability, as well as the interaction between neutrophils and monocyte-macrophages.

Keywords: Atherosclerosis; foam cells; innate inflammation; macrophages; plaque stability.