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Lookup NU author(s): Dr Luke Spray, Dr Catherine Park, Dr Suzanne Cormack, Dr Ashfaq Mohammed, Dr Stephen Boag, Dr Karim Bennaceur, Dr Kateryna Sopova, Professor Gavin RichardsonORCiD, Professor Konstantinos StellosORCiD, Professor Ioakim SpyridopoulosORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Aims: Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).Methods and Results: We retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling.Conclusion: We show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.
Author(s): Spray L, Park C, Cormack S, Mohammed A, Panahi P, Boag S, Bennaceur K, Sopova K, Richardson G, Stangl V, Rech L, Rainer P, Ramos G, Hofmann U, Stellos K, Spyridopoulos I
Publication type: Article
Publication status: Published
Journal: Frontiers in Immunology
Year: 2021
Volume: 12
Online publication date: 05/05/2021
Acceptance date: 20/04/2021
Date deposited: 12/05/2021
ISSN (electronic): 1664-3224
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/fimmu.2021.605857
DOI: 10.3389/fimmu.2021.605857
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