Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study

Tucker, Bradley; Kurup, Rahul; Barraclough, Jennifer; Henriquez, Rodney; Cartland, Sian; Arnott, Clare; Misra, Ashish; Martinez, Gonzalo; Kavurma, Mary; Patel, Sanjay

Abstract

Purpose: Existing literature reports that colchicine inhibits inflammasome activation and downstream inflammatory cytokine production and stabilizes coronary plaque. However, colchicine's effect on chemokines, which orchestrate multiple atheroinflammatory pathways, is unknown. Methods: Patients with acute coronary syndrome (ACS) were randomly assigned to colchicine (1.5 mg PO) (n = 12; mean age, 65.2 years) or no treatment (n = 13; mean age, 62.2 years). Blood samples were collected during cardiac catheterization within 24 hours of colchicine administration from the coronary sinus, aortic root, and right atrium. Patients with colchicine-naive stable angina (SAP) (n = 13; mean age, 66.8 years) were additionally sampled. Serum chemokine levels were analyzed with ELISA. In parallel, monocytes from healthy donors were isolated and subjected to colchicine treatment. Findings: Transcoronary (TC) levels of chemokine ligand 2 (CCL2) and C-X3-C motif chemokine ligand 1 (CX3CL1) were significantly elevated in patients with ACS versus patients with SAP (P < 0.01). TC chemokine ligand 5 (CCL5) levels were not significantly (P = 0.084) elevated in patients with ACS versus patients with SAP. Colchicine treatment markedly reduced TC levels of CCL2, CCL5, and CX3CL1 in patients with ACS (P < 0.05). In vitro colchicine suppressed CCL2 gene expression in stimulated monocytes (P < 0.05). Colchicine treatment reduced the intracellular concentration of all 3 chemokines (P < 0.01) and impaired monocyte chemotaxis (P < 0.05). (C) 2019 Published by Elsevier Inc.

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Título según WOS: Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study
Título según SCOPUS: Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study
Título de la Revista: CLINICAL THERAPEUTICS
Volumen: 41
Número: 10
Editorial: Elsevier
Fecha de publicación: 2019
Página de inicio: 2172
Página final: 2181
Idioma: English
DOI:

10.1016/j.clinthera.2019.07.015

Notas: ISI, SCOPUS