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

Objective Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) 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 use in patients with coronary disease. However, its effects on post-PCI NET formation in ACS has not been explored. Approach and Results 60 patients (40 ACS; 20 stable angina pectoris [SAP]) were prospectively recruited and allocated to colchicine or no treatment. Within 24 h of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 ACS patients post-PCI and 4 healthy controls were treated in vitro with colchicine (25 nM) and stimulated with either ionomycin (5 μM) or phorbol 12-myristate 13-acetate (PMA, 50 nM). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst and anti-alpha tubulin. Baseline characteristics were similar across both treatment and control arms. ACS patients had higher NET release versus SAP patients (p<0.001), which was reduced with colchicine treatment (AUC: 0.58 vs. 4.29; p<0.001). In vitro , colchicine suppressed spontaneous (p=0.004), PMA-induced (p=0.03) and ionomycin-induced (p=0.02) NET formation in neutrophils isolated from ACS patients post-PCI, but not healthy controls. Tubulin organisation was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. Conclusions Colchicine suppresses NET formation in ACS patients post-PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomised trials powered for clinical endpoints. Graphical Abstract