Macrophage Dynamics in Atherosclerotic Pathogenesis

Atherosclerosis arises from the chronic accumulation of lipids and inflammatory cells within the arterial wall, initiating with endothelial dysfunction and monocyte recruitment. Circulating monocytes migrate into the intima and differentiate into macrophages, where they adopt distinct functional states in response to local cues. These macrophages internalise modified lipoproteins via scavenger receptors, leading to lipid overload and the formation of foam cells. Foam cell accumulation drives plaque growth, necrotic core formation and destabilisation through impaired efferocytosis, sustained cytokine release and matrix metalloproteinase activity. Macrophage phenotypes range from pro-inflammatory (often termed M1-like) to reparative (M2-like), with dynamic interconversion regulated by lipid metabolites, growth factors and mechanical stimuli. Cholesterol efflux pathways mediated by ATP-binding cassette transporters balance uptake processes and influence lesion regression. Beyond foam-cell biology, macrophages shape neovascularisation, calcification and fibrous cap integrity through paracrine interactions with smooth muscle cells and endothelial cells. Therapeutic strategies now target lipid handling, inflammatory signalling and resolution pathways to modulate macrophage function and stabilise plaques.

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Macrophage Dynamics in Atherosclerotic Pathogenesis publication trend

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Technical terms

Macrophage polarisation: The process by which macrophages adopt distinct functional programmes (pro-inflammatory or reparative) in response to microenvironmental signals.

Foam cell: A lipid-laden macrophage containing abundant intracellular lipid droplets, characteristic of early atherosclerotic lesions.

Scavenger receptor: A class of membrane receptors on macrophages that mediate uptake of modified lipoproteins and damaged cellular debris.

Efferocytosis: The phagocytic clearance of apoptotic cells by macrophages, essential for resolution of inflammation and plaque stability.

References

1. Triacylglycerol uptake and handling by macrophages: From fatty acids to lipoproteins. Progress in Lipid Research (2023).
2. Hypertensive Pressure Mechanosensing Alone Triggers Lipid Droplet Accumulation and Transdifferentiation of Vascular Smooth Muscle Cells to Foam Cells. Advanced Science (2023).
3. Scavenger Receptors Class A-I/II and CD36 Are the Principal Receptors Responsible for the Uptake of Modified Low Density Lipoprotein Leading to Lipid Loading in Macrophages*. Journal of Biological Chemistry (2002).
4. Macropinocytosis Is the Endocytic Pathway That Mediates Macrophage Foam Cell Formation with Native Low Density Lipoprotein*. Journal of Biological Chemistry (2004).