Transient miR-92a Induction in Intermediate Monocytes (CD14++CD16+) in Acute Coronary Syndrome (ACS)
Lukas Harbaum1, Julian Kreutz1, Carina Weibler1
1Department of Cardiology, Angiology and Intensive Care Medicine, Philipps-Universität Marburg, Baldingerstrasse, 35043 Marburg, Germany.
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 (T0P) and from the culprit coronary artery (T0C) during catheterization. Additional peripheral samples were collected 48 h after intervention (T1) and at the 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 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 T1 compared with baseline (T0p) and the 3-month follow-up (T2). 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.
Insights
MicroRNA-92a (miR-92a) expression temporarily increased in intermediate monocytes of acute coronary syndrome (ACS) patients post-intervention. This finding suggests a dynamic role for miR-92a in monocyte subsets during ACS recovery.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Intermediate monocytes (CD14++CD16+) are pro-inflammatory and implicated in acute coronary syndrome (ACS) plaque vulnerability.
- MicroRNA-92a (miR-92a) promotes vascular inflammation and endothelial dysfunction by targeting Kruppel-like factors (KLFs).
- Both intermediate monocytes and miR-92a are linked to atherosclerotic plaque instability.
Purpose of the Study:
- To investigate differential regulation of miR-92a in monocyte subpopulations between ACS and chronic coronary syndrome (CCS) patients.
- To assess miR-92a expression in peripheral and intracoronary monocyte subsets over time post-intervention in ACS.
Main Methods:
- Monocyte subpopulations (classical, intermediate, non-classical) were sorted from peripheral blood of ACS and CCS patients using fluorescence-activated cell sorting (FACS).
- miR-92a expression was quantified using real-time PCR at multiple time points: baseline (peripheral and coronary), 48 hours post-intervention, and 3-month follow-up.
- Expression levels were compared between ACS and CCS cohorts and across different monocyte subsets and time points.
Main Results:
- miR-92a levels were stable in classical and non-classical monocytes and did not differ between ACS and CCS patients.
- No significant spatial gradient of miR-92a expression was found between intracoronary and peripheral samples at baseline.
- Intermediate monocytes in ACS patients exhibited a transient increase in miR-92a expression at 48 hours post-intervention compared to baseline and 3-month follow-up.
Conclusions:
- A transient alteration in miR-92a expression occurs specifically in intermediate monocytes during the early post-interventional phase of ACS.
- This temporal change in miR-92a in intermediate monocytes warrants further investigation in larger cohorts to confirm its biological significance in ACS pathogenesis.
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