Monocyte-Endothelial Cell Interactions in Atherosclerosis

Atherosclerosis is driven by a complex interplay between circulating monocytes and the vascular endothelium. Endothelial cells lining the arterial wall respond to risk factors such as hyperlipidaemia, hypertension and smoking by upregulating adhesion molecules and secreting chemokines. Circulating monocytes tether and roll along activated endothelium via selectins, then adhere firmly through integrin engagement. Subsequent transmigration into the intima is guided by chemokine gradients, where monocytes differentiate into macrophages and foam cells upon uptake of oxidised lipids. This local accumulation of foam cells and secretion of pro-inflammatory cytokines perpetuates endothelial dysfunction, promotes plaque growth and heightens the risk of plaque rupture. Interventions that modulate adhesion molecule expression, chemokine signalling or monocyte differentiation are under intense investigation as strategies to stabilise or regress atherosclerotic lesions.

Research from Nature Portfolio

Recent work has demonstrated that sustained antagonism of the CC chemokine receptor CCR2 markedly reduces monocyte recruitment and atherosclerotic burden in preclinical models. A novel small-molecule CCR2 antagonist with high receptor residence time achieved prolonged CCR2 occupancy in apoE-deficient mice, lowering circulating CCR2+ monocytes and plaque size in the carotid artery and aortic root. These findings underscore the importance of achieving durable chemokine receptor blockade to interrupt monocyte homing to inflamed endothelium and highlight CCR2 as a viable therapeutic target in atherosclerosis.

Monocyte-Endothelial Cell Interactions in Atherosclerosis publication trend

The graph below shows the total number of articles in monocyte-endothelial cell interactions in atherosclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Monocyte: A type of circulating white blood cell that adheres to and migrates through the endothelium to become a macrophage within vessel walls.

Endothelial cell: The specialised cells forming the inner lining of blood vessels, which regulate vascular tone, permeability and leukocyte recruitment.

Adhesion molecules: Cell-surface proteins (such as selectins and integrins) that mediate the sequential steps of leukocyte rolling, arrest and firm adhesion on endothelium.

Chemokine: A small cytokine that creates a chemical gradient to direct the migration of immune cells, including monocytes, toward sites of inflammation.

Transmigration (Diapedesis): The process by which leukocytes actively migrate across the endothelial barrier into the underlying tissue.

Foam cell: A lipid-laden macrophage formed after extensive uptake of oxidised low-density lipoprotein, contributing to plaque formation and instability.

References

1. A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy. Scientific Reports (2017).
2. Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment. Cell Communication and Signaling (2024).
3. Chemokines and their receptors in Atherosclerosis. Journal of Molecular Medicine (2015).