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Published on: October 17, 2017
A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture
Ramona Vinci1, Daniela Pedicino1,2, Alice Bonanni1
1Department of Cardiovascular and Pneumological Sciences, Catholic University of the Sacred Heart, Rome, Italy.
Insights
Monocyte subsets in acute coronary syndrome (ACS) patients differ based on plaque rupture versus erosion. A novel pre-classical monocyte population was identified in ACS patients with ruptured plaques, indicating distinct disease mechanisms.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Biochemistry
Background:
- Acute coronary syndrome (ACS) involves complex inflammatory processes.
- Monocyte subsets play a critical role in atherosclerosis.
- Plaque morphology (rupture vs. erosion) influences ACS outcomes, but monocyte subset distribution remains unexplored.
Purpose of the Study:
- To investigate differences in circulating monocyte subset frequencies in non-ST-elevation ACS (NSTE-ACS) patients compared to chronic coronary syndrome (CCS) patients.
- To correlate monocyte subset distribution with culprit coronary plaque morphology (rupture vs. erosion) assessed by optical coherence tomography (OCT).
- To explore the functional response of monocytes to lipopolysaccharide (LPS) stimulation in NSTE-ACS patients.
Main Methods:
- Flow cytometry was used to analyze monocyte subsets (classical, intermediate, non-classical) based on CD14 and CD16 expression in 74 NSTE-ACS patients and 30 CCS controls.
- OCT was performed on 21 NSTE-ACS patients to characterize culprit plaque morphology and assess macrophage infiltration (MØI).
- Peripheral blood mononuclear cells (PBMCs) from NSTE-ACS patients were stimulated with LPS to quantify inflammatory cytokine (IL-1β, IL-6, IL-10) release.
Main Results:
- Monocyte subset distribution showed a distinct signature in NSTE-ACS patients with ruptured fibrous cap (RFC) plaques compared to those with plaque erosion.
- NSTE-ACS patients with RFC exhibited heightened LPS-mediated release of IL-1β, IL-6, and IL-10.
- A novel 'pre-classical' monocyte population (PCM: CD14+CD16-) was identified and found to be more prevalent in NSTE-ACS patients, particularly those with RFC and MØI.
Conclusions:
- Circulating monocyte subset distribution serves as a biological signature differentiating ACS pathophysiology based on plaque rupture versus erosion.
- Patients with ruptured plaques display heightened inflammatory responses to LPS stimulation.
- The newly identified PCM population may represent a key player in ACS pathogenesis, especially in cases of plaque rupture with significant macrophage infiltration.
Abstract:
The evaluation of monocyte subset distribution among acute coronary syndrome (ACS) patients according to culprit coronary plaque morphology has never been explored. We evaluated whether there were significant differences in frequency of circulating monocyte subsets isolated from ACS patients according to optical coherence tomography (OCT) investigation of plaque erosion and rupture. We enrolled 74 patients with non-ST-elevation ACS (NSTE-ACS), 21 of them underwent OCT investigation of the culprit coronary plaque and local macrophage infiltration (MØI) assessment. As control, we enrolled 30 chronic coronary syndrome (CCS) patients. We assessed the frequency of monocyte subsets in the whole study population, in reliance on their CD14 and CD16 expression (classical, CM: CD14++CD16-; intermediates, IM: CD14++CD16+; non-classical, NCM: CD14+CD16++). Then, we tested the effect of lipopolysaccharide (LPS) (a CD14 ligand) on peripheral blood mononuclear cells (PBMCs) of NSTE-ACS patients, quantifying the inflammatory cytokine levels in cell-culture supernatants. Our data proved that monocyte subsets isolated from NSTE-ACS patients represent a peculiar biological signature of the pathophysiological mechanism lying beneath atherosclerotic plaque with a ruptured fibrous cap (RFC) as compared with plaque erosion. Moreover, the magnitude of LPS-mediated effects on IL-1β, IL-6, and IL-10 cytokine release in cell-culture supernatants appeared to be greater in NSTE-ACS patients with RFC. Finally, we described a fourth monocyte population never explored before in this clinical setting (pre-classical monocytes, PCM: CD14+CD16-) that was prevalent in NSTE-ACS patients as compared with CCS and, especially, in patients with RFC and culprit plaque with MØI.
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