Transient miR-92a Induction in Intermediate Monocytes (CD14(++)CD16(+)) in Acute Coronary Syndrome (ACS)

急性冠脉综合征(ACS)中中间单核细胞(CD14(++)CD16(+))中miR-92a的瞬时诱导

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Abstract

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 Kruppel-like factors (KLFs) 2/4, thereby inducing endothelial dysfunction and increasing leukocyte adhesion. Because both intermediate monocytes and miR-92a contribute to plaque instability, their expression profiles appear relevant in acute ischemia. We investigated whether miR-92a is differentially regulated in monocyte subpopulations in ACS compared to chronic coronary syndrome (CCS). Patients with ACS (STEMI/NSTEMI) undergoing urgent coronary angiography and patients with CCS were enrolled. Blood samples were collected peripherally (T(0P)) and from the culprit coronary artery (T(0C)) during catheterization. Additional peripheral samples were collected 48 h after intervention (T(1)) and at the 3-month follow-up (T(2)). 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 analyzed across predefined time points. In classical and non-classical monocytes, miR-92a levels remained stable throughout the observation period and did not differ between ACS and CCS patients. No spatial expression gradient was observed between intracoronary and peripheral samples at baseline. In contrast, intermediate monocytes in the ACS cohort showed a transient increase in miR-92a expression at T(1) compared with baseline (T(0p)) and the 3-month follow-up (T(2)). No comparable temporal changes were observed in CCS patients. These findings indicate a temporary alteration of miR-92a expression in intermediate monocytes during the early post-interventional phase following ACS. However, given the exploratory nature of this study and the limited sample size, the biological significance of this observation requires confirmation in larger cohorts.

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