Summary. Aim: Monocytes contribute to both myocardial damage and repair by virtue of subset heterogeneity. The dynamics and functional characteristics of the three human monocyte subsets, including the unique CD14++CD16+ subset, and their contributions to monocyte platelet aggregates (MPAs) following ST-elevation myocardial infarction (STEMI) are unknown. We aimed to examine dynamic changes and relation to left ventricular ejection fraction (LVEF) of the three human monocyte subsets and their aggregates with platelets following STEMI. Methods: Three monocyte subsets, CD14++CD16)CCR2+ (ÔclassicalÕ, Mon1), CD14++CD16+CCR2+ (ÔintermediateÕ, Mon2) and CD14+CD16++CCR2) (Ônon-classicalÕ, Mon3), and their contribution to MPAs were analyzed by flow cytometry in 50 patients with STEMI, 40 patients with stable coronary artery disease (CAD) and 40 healthy volunteers. Study parameters were measured within 24 h of primary percutaneous coronary intervention (PCI) (day1) and on days 3, 7 and 30. Monocyte activation was assessed by measuring the nuclear factor jB (NFjB) pathway. LVEF was assessed 6 weeks after STEMI. Correlations between monocyte subsets/MPAs and plasma cytokines and troponin were assessed. Results: We observed marked differences in subset dynamics, with a prominent increase in Mon2 (P < 0.0001) but no changes in Mon3. Significant increases in Mon2 CD14 (P = 0.002) and CCR2 (P < 0.0001) expression, and reduction in CD16 expression (P = 0.001) were seen. NFjB pathway activity increased most prominently in Mon2 (P = 0.007). Mon2 count correlated with peak troponin (r = 0.31, P = 0.04) and plasma interleukin (IL)-6 (r = 0.65, P < 0.0001) and IL-10 (r = 0.34, P = 0.017). Mon1 correlated with IL-6 (r = 0.55, P < 0.0001). Reduced Mon2 expression of CD16 on day 1 was independently predictive of higher LVEF (b = )0.37, P = 0.013). The increase in MPA count following STEMI persisted at 1 month. Conclusion: The Mon2 ÔintermediateÕ subset has unique dynamic and functional characteristics following STEMI and significant correlations with troponin, plasma cytokines and convalescent left ventricular function. The persistent increase in MPA count 30 days after STEMI may affect monocyte subset functional activity.

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The CD40-CD40L system is a pathway which is associated with both prothrombotic and proinflammatory effects. CD40 and its ligand were first discovered on the surface of activated T cells, but its presence on B cells, antigen-presenting cells, mast cells, and finally platelets, is evident. The soluble form of CD40L (sCD40L) is derived mainly from activated platelets and contributes to the pathophysiology of atherosclerosis and atherothrombosis. Indeed, sCD40L has autocrine, paracrine, and endocrine activities, and it enhances platelet activation, aggregation, and platelet-leucocyte conjugation that may lead to atherothrombosis. It has even been suggested that sCD40L may play a pathogenic role in triggering acute coronary syndromes. Conversely, blockade of this pathway with anti-CD40L antibodies may prevent or delay the progression of atherosclerosis. Concentrations of sCD40L also predict risk of future cardiovascular disease in healthy women and clinical outcomes in patients with acute coronary syndromes. However, there are controversial and uncertain points over the application of this biomarker to clinical cardiology. In this review, we provide an overview of potential implications of CD40-CD40L signalling and sCD40L as a biomarker in patients with atherosclerotic vascular diseases.