Monocyte Subsets in Cardiovascular Health and Disease

Monocytes are key mediators of vascular immunity and tissue repair, circulating as three subsets defined by CD14 and CD16 expression. Classical monocytes (CD14++CD16–) patrol the bloodstream, phagocytose pathogens and differentiate into macrophages or dendritic cells at sites of injury. Intermediate monocytes (CD14++CD16+) exhibit heightened inflammatory potential, produce cytokines and chemokines that drive plaque formation and are elevated in advanced vascular lesions. Non-classical monocytes (CD14+CD16++) patrol the endothelium, sense injury and secrete pro-inflammatory mediators such as tumour necrosis factor to regulate endothelial activation. Dysregulation of these subsets contributes to atherosclerosis, peripheral artery disease and post-infarct remodelling. Recent advances reveal significant intra-subset and interindividual heterogeneity shaped by environmental and metabolic cues, informing biomarker development and immunomodulatory strategies in cardiovascular disease.

Research from Nature Portfolio

Recent studies in peripheral artery occlusive disease have demonstrated a stage-dependent expansion of intermediate monocytes characterised by upregulated adhesion molecules and reactive oxygen species generation, identifying this subset as both a biomarker and potential therapeutic target in advanced vascular stenosis. An experimental human endotoxaemia model of low-grade inflammation has shown that intermediate monocytes mount the strongest response to systemic lipopolysaccharide challenge, with rapid integrin activation and pro-inflammatory transcript induction, followed by activation of non-classical monocytes, whereas classical monocytes display limited short-term activation. These findings highlight the dynamic plasticity of monocyte subsets under inflammatory stress and their relevance to vascular injury and repair.

Monocyte Subsets in Cardiovascular Health and Disease publication trend

The graph below shows the total number of articles in monocyte subsets in cardiovascular health and disease across all publications each year (not limited to Nature Index journals).

Technical terms

Classical monocytes (CD14++CD16–): The predominant blood monocyte subset involved in phagocytosis and differentiation into macrophages and dendritic cells.

Intermediate monocytes (CD14++CD16+): A transitional subset with elevated inflammatory cytokine production linked to vascular inflammation and lesion progression.

Non-classical monocytes (CD14+CD16++): A patrolling subset that monitors endothelial integrity and secretes pro-inflammatory mediators upon vascular injury.

Atherosclerosis: A chronic inflammatory disease of arterial walls marked by lipid accumulation, foam cell formation and fibrous cap development.

Endotoxaemia: The systemic presence of bacterial lipopolysaccharide, used experimentally to model low-grade inflammation in vivo.

References

1. Monocyte Differentiation and Heterogeneity: Inter-Subset and Interindividual Differences. International Journal of Molecular Sciences (2023).
2. The “Intermediate” CD14++CD16+ monocyte subset increases in severe peripheral artery disease in humans. Scientific Reports (2016).
3. Differential in vivo activation of monocyte subsets during low-grade inflammation through experimental endotoxemia in humans. Scientific Reports (2016).
4. A Single-Cell Gene-Expression Profile Reveals Inter-Cellular Heterogeneity within Human Monocyte Subsets. PLOS ONE (2015).
5. Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Frontiers in Immunology (2019).
6. Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface. The Journal of Immunology (2017).