Blake J. Cochran, Australia

University of New South Wales School of Medical Sciences

Presenter of 1 Presentation

Colchicine inhibits neutrophil extracellular trap formation in acute coronary syndrome patients post percutaneous coronary intervention

Session Type
Track 4 - Prevention and Treatment of CVD
Date
05.10.2020, Monday
Session Time
10:00 - 11:13
Lecture Time
10:50 - 11:00

Abstract

Background and Aims

Release of neutrophil extracellular traps (NETs) after PCI in ACS patients is associated with peri-procedural myocardial infarction, as a result of microvascular obstruction via pro-inflammatory and pro-thrombotic pathways. Colchicine is a potent, well-established anti-inflammatory agent with growing evidence to support its use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS patients is unknown.

Methods

60 patients (40 ACS; 20 stable angina pectoris [SAP]) were prospectively recruited and allocated to colchicine (1.5 mg) or no treatment. Within 24 h of treatment, serial coronary sinus blood samples were collected during PCI for quantification of NETosis. Isolated neutrophils from 10 ACS patients post-PCI and 4 healthy controls were treated with colchicine (25 nM) and stimulated with either ionomycin (5 mM) or PMA (50 nM) in vitro. Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst and anti-alpha tubulin.

Results

Untreated ACS patients had higher NET release post-PCI, versus untreated SAP patients (p<0.001). In ACS patients, colchicine treatment resulted in suppression of NETosis versus control (AUC 0.58 vs. 4.29; p<0.001); a phenomenon that was not observed in SAP patients. In vitro, colchicine suppressed spontaneous (p=0.004), PMA-induced (p=0.05) and ionomycin-induced (p=0.02) NETosis in neutrophils from ACS patients, but not healthy controls. Colchicine caused alteration to the neutrophil microtubule complex, inhibiting release of DNA.

Conclusions

Colchicine suppresses NET formation in ACS patients post-PCI and is independent of classic NET signalling pathways. These findings warrant further investigation in randomised trials powered for clinical endpoints.

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