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Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention

BACKGROUND: Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro‐inflammatory and prothrombotic pathways. Colchicine i...

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Autores principales: Vaidya, Kaivan, Tucker, Bradley, Kurup, Rahul, Khandkar, Chinmay, Pandzic, Elvis, Barraclough, Jennifer, Machet, Joshua, Misra, Ashish, Kavurma, Mary, Martinez, Gonzalo, Rye, Kerry‐Anne, Cochran, Blake J., Patel, Sanjay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955504/
https://www.ncbi.nlm.nih.gov/pubmed/33346683
http://dx.doi.org/10.1161/JAHA.120.018993
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author Vaidya, Kaivan
Tucker, Bradley
Kurup, Rahul
Khandkar, Chinmay
Pandzic, Elvis
Barraclough, Jennifer
Machet, Joshua
Misra, Ashish
Kavurma, Mary
Martinez, Gonzalo
Rye, Kerry‐Anne
Cochran, Blake J.
Patel, Sanjay
author_facet Vaidya, Kaivan
Tucker, Bradley
Kurup, Rahul
Khandkar, Chinmay
Pandzic, Elvis
Barraclough, Jennifer
Machet, Joshua
Misra, Ashish
Kavurma, Mary
Martinez, Gonzalo
Rye, Kerry‐Anne
Cochran, Blake J.
Patel, Sanjay
author_sort Vaidya, Kaivan
collection PubMed
description BACKGROUND: Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro‐inflammatory and prothrombotic pathways. Colchicine is a 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 have not been explored. METHODS AND RESULTS: Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post‐PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 μmol/L) or phorbol 12‐myristate 13‐acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti‐alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris (P<0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; P<0.001). In vitro, colchicine suppressed unstimulated (P<0.001), phorbol 12‐myristate 13‐acetate–induced (P=0.009) and ionomycin‐induced (P=0.002) NET formation in neutrophils isolated from patients with ACS post‐PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. CONCLUSIONS: Colchicine suppresses NET formation in patients with ACS post‐PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. REGISTRATION: URL: https://anzctr.org.au; Unique identifier: ACTRN12619001231134.
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spelling pubmed-79555042021-03-17 Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention Vaidya, Kaivan Tucker, Bradley Kurup, Rahul Khandkar, Chinmay Pandzic, Elvis Barraclough, Jennifer Machet, Joshua Misra, Ashish Kavurma, Mary Martinez, Gonzalo Rye, Kerry‐Anne Cochran, Blake J. Patel, Sanjay J Am Heart Assoc Original Research BACKGROUND: Release of neutrophil extracellular traps (NETs) after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is associated with periprocedural myocardial infarction, as a result of microvascular obstruction via pro‐inflammatory and prothrombotic pathways. Colchicine is a 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 have not been explored. METHODS AND RESULTS: Sixty patients (40 ACS; 20 stable angina pectoris) were prospectively recruited and allocated to colchicine or no treatment. Within 24 hours of treatment, serial coronary sinus blood samples were collected during PCI. Isolated neutrophils from 10 patients with ACS post‐PCI and 4 healthy controls were treated in vitro with colchicine (25 nmol/L) and stimulated with either ionomycin (5 μmol/L) or phorbol 12‐myristate 13‐acetate (50 nmol/L). Extracellular DNA was quantified using Sytox Green and fixed cells were stained with Hoechst 3342 and anti‐alpha tubulin. Baseline characteristics were similar across both treatment and control arms. Patients with ACS had higher NET release versus patients with stable angina pectoris (P<0.001), which was reduced with colchicine treatment (area under the curve: 0.58 versus 4.29; P<0.001). In vitro, colchicine suppressed unstimulated (P<0.001), phorbol 12‐myristate 13‐acetate–induced (P=0.009) and ionomycin‐induced (P=0.002) NET formation in neutrophils isolated from patients with ACS post‐PCI, but not healthy controls. Tubulin organization was impaired in neutrophils from patients with ACS but was restored by colchicine treatment. CONCLUSIONS: Colchicine suppresses NET formation in patients with ACS post‐PCI by restoring cytoskeletal dynamics. These findings warrant further investigation in randomized trials powered for clinical end points. REGISTRATION: URL: https://anzctr.org.au; Unique identifier: ACTRN12619001231134. John Wiley and Sons Inc. 2020-12-21 /pmc/articles/PMC7955504/ /pubmed/33346683 http://dx.doi.org/10.1161/JAHA.120.018993 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Vaidya, Kaivan
Tucker, Bradley
Kurup, Rahul
Khandkar, Chinmay
Pandzic, Elvis
Barraclough, Jennifer
Machet, Joshua
Misra, Ashish
Kavurma, Mary
Martinez, Gonzalo
Rye, Kerry‐Anne
Cochran, Blake J.
Patel, Sanjay
Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title_full Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title_fullStr Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title_full_unstemmed Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title_short Colchicine Inhibits Neutrophil Extracellular Trap Formation in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention
title_sort colchicine inhibits neutrophil extracellular trap formation in patients with acute coronary syndrome after percutaneous coronary intervention
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955504/
https://www.ncbi.nlm.nih.gov/pubmed/33346683
http://dx.doi.org/10.1161/JAHA.120.018993
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