Macrophage metabolic reprogramming and atherosclerotic plaque microenvironment: Fostering each other?

Macrophages are the central immune cells in atherosclerosis (AS) and play a critical role in the initiation, progression and invasion of atherosclerotic plaques. Metabolic reprogramming is a crucial feature that determines macrophage function and is driven by a combination of intrinsic alterations in macrophages and extrinsic factors such as cytokines acting in the plaque microenvironment. Intrinsic macrophage mechanisms activate signal transduction pathways that change metabolic enzyme activity, and the expression of metabolic regulators. Extrinsic signalling mechanisms involve lipids and cytokines in the microenvironment, promoting and amplifying macrophage metabolic reprogramming. This review describes the intrinsic and extrinsic mechanisms driving macrophage metabolic reprogramming in the AS microenvironment and the interplay of these metabolic rewires in the microenvironment. Moreover, we discuss whether targeting these different pathways to treat macrophage microenvironmental changes can alter the fate of the vulnerable plaques.

Automated summary

Macrophages play a crucial role in the initiation, progression, and invasion of atherosclerotic plaques in atherosclerosis (AS). Metabolic reprogramming, driven by intrinsic macrophage alterations and extrinsic factors, determines macrophage function. Intrinsic mechanisms involve signal transduction pathways and metabolic enzyme activity, while extrinsic mechanisms involve lipids and cytokines in the plaque microenvironment. Targeting these pathways may alter the fate of vulnerable plaques.