Platelet Dynamics in Atherosclerotic Disease

Platelets, long recognised for their role in haemostasis, are now appreciated as active participants in all stages of atherosclerosis. In the early lesion they adhere to activated endothelium, secrete chemokines and growth factors, and recruit monocytes and lymphocytes. Lipid‐laden platelets further oxidise low-density lipoproteins (LDL), amplifying local inflammation and foam cell formation. Within established plaques, platelet–leukocyte aggregates and microparticles perpetuate endothelial dysfunction, while platelet-driven thrombin generation primes the site for acute thrombotic complications upon plaque rupture. Beyond aggregation, dynamic changes in platelet receptor expression and intracellular signalling modulate responses to disturbed flow, hyperlipidaemia and oxidative stress, linking metabolic risk factors to inflammatory and thrombotic processes. Therapeutic modulation of these pathways holds promise for both stabilising plaques and preventing arterial occlusion.

Research from Nature Portfolio

Work has revealed that the chemokine platelet factor 4 (PF4, also known as CXCL4) is not merely a passive inflammatory mediator but functions as an agonist of the CC-class chemokine receptor CCR1 on monocytes. PF4 binding induces CCR1 endocytosis and elicits calcium-dependent chemotaxis, thereby promoting monocyte recruitment under flow conditions. This discovery identifies CCR1 as a critical receptor linking platelet activation to monocyte homing in inflamed vessels and suggests targeting PF4–CCR1 interactions as a novel approach to modulate early atherogenic cell trafficking.

Platelet Dynamics in Atherosclerotic Disease publication trend

The graph below shows the total number of articles in platelet dynamics in atherosclerotic disease across all publications each year (not limited to Nature Index journals).

Technical terms

Platelet factor 4 (PF4): A chemokine released from platelet α-granules that modulates leukocyte recruitment and lipoprotein interactions.

CCR1: A G protein-coupled receptor on monocytes that mediates chemotaxis in response to CC-class chemokines, including PF4.

Scavenger receptors: Platelet surface proteins (e.g. CD36) that bind modified lipoproteins and transduce pro-inflammatory signalling.

Oxidised low-density lipoprotein (oxLDL): LDL particles modified by oxidative processes, which strongly activate platelets and contribute to foam cell formation.

Cyclic-nucleotide pathways: Intracellular signalling cascades (cAMP, cGMP) that normally inhibit platelet activation and are suppressed by atherogenic stimuli.

References

1. Platelets as an inter‐player between hyperlipidaemia and atherosclerosis. Journal of Internal Medicine (2024).
2. CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific Reports (2018).
3. Platelets, a Key Cell in Inflammation and Atherosclerosis Progression. Cells (2022).
4. Oxidised Low-Density Lipoprotein-Induced Platelet Hyperactivity—Receptors and Signalling Mechanisms. International Journal of Molecular Sciences (2022).