A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture.

Filippo Crea,Giovanna Liuzzo,Francesco Cribari,Pellegrino Ciampi,Carlo Trani,Daniela Pedicino,Francesco Canonico,Massimo Massetti,Anna Severino,Eugenia Pisano,Myriana Ponzo,Rocco Antonio Montone,Ramona Vinci,Cristina Conte,Alice Bonanni,Alessia D’Aiello,Giulio Russo,Maria Chiara Grimaldi,Marianna Di Sario

doi:10.3389/fcell.2021.753223

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.

Highlights

Innate immunity activation represents a key mechanism in the pathogenesis of acute coronary syndromes (ACS), involved in the onset and progression of the atherosclerotic plaques (Shalhoub et al, 2011)
Analysis of the distribution of circulating monocyte subsets according to their CD14 and CD16 surface expression led to the identification of a fourth monocyte population other than the three already known subsets
When monocyte subset distribution was evaluated in the whole study population, the newly identified pre-classical monocyte (PCM) subset was more frequent in NSTE-ACS rather than in chronic coronary syndrome (CCS) patients

Summary

Introduction

Innate immunity activation represents a key mechanism in the pathogenesis of acute coronary syndromes (ACS), involved in the onset and progression of the atherosclerotic plaques (Shalhoub et al, 2011). Among the innate immunity cells, monocytes are the most plastic and dynamic ones, being able to switch toward several functional phenotypes (Canè et al, 2019). Monocyte Subset Distribution and Plaque Rupture two-thirds of ACS patients presenting with plaque rupture at optical coherence tomography (OCT) investigation had evidence of plaque macrophage infiltration (MØI) and raised systemic levels of inflammatory biomarkers (Scalone et al, 2017). In ACS patients with ruptured fibrous cap (RFC), monocytederived macrophages display thrombotic and inflammatory activity (Fracassi et al, 2021). Our purpose was to evaluate monocyte subset distribution in NSTE-ACS patients according to OCT identification of plaque rupture and erosion

Methods

Results

Discussion

Conclusion