Background
Intermediate monocytes (CD14++CD16+), a highly pro-inflammatory subset, are linked to endothelial activation, thrombus formation, and poor outcomes in acute coronary syndrome (ACS), suggesting a role in the transition to plaque vulnerability. MicroRNA-92a (miR-92a) promotes vascular inflammation by repressing the transcription factors KLF2/KLF4, resulting in endothelial dysfunction and increased leukocyte adhesion. As both intermediate monocytes and miR-92a contribute to plaque instability, their expression profile appears relevant in acute ischemia. We investigated whether miR-92a is differentially regulated in monocyte subpopulations in ACS compared to chronic coronary syndrome (CCS).
Methods
Patients with ACS (STEMI/NSTEMI) undergoing urgent coronary angiography and patients with CCS as controls were enrolled prospectively. Blood samples were collected peripherally (T₀p) and from the culprit coronary artery (T₀c) during catheterization. Additional peripheral samples were collected 48 hours after intervention (T₁) and at 3-month follow-up (T₂). Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density-gradient centrifugation. Monocytes were sorted by fluorescence-activated cell sorting (FACS) into classical (CD14++CD16–), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) subsets. miR-92a expression was measured using real-time PCR and compared across groups at each time point.
Results
In classical and non-classical monocytes, miR-92a levels stayed consistent at all time points. These levels also did not differ between ACS and CCS groups. There was no spatial expression gradient between the culprit artery and peripheral samples. In contrast, miR-92a expression levels in intermediate monocytes from ACS patients showed a significant, temporary increase at T₁ compared to CCS controls (p < 0.01). Levels then returned to baseline at T₂.
Conclusion and Perspectives
These findings suggest that intermediate monocytes might be a key source of miR-92a in the early post-ischemic inflammation of ACS. The temporary nature of this response suggests that miR-92a upregulation may be a marker of acute inflammatory activation. Ongoing research aims to clarify whether it could be effectively targeted for therapy.
