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SHR Neuro Cancer Cardio Lipid Metab Microb

Spray, L; Park, C; Cormack, S; Mohammed, A; Panahi, P; Boag, S; Bennaceur, K; Sopova, K; Richardson, G; Stangl, VM; Rech, L; Rainer, PP; Ramos, GC; Hofmann, U; Stellos, K; Spyridopoulos, I.
The Fractalkine Receptor CX₃CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling.
Front Immunol. 2021; 12: 605857-605857. Doi: 10.3389/fimmu.2021.605857 [OPEN ACCESS]
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Co-authors Med Uni Graz: Rainer Peter; Rech Cara Lavinia Shirin; Stangl Verena Maria
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Abstract:: 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). 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. 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. Copyright © 2021 Spray, Park, Cormack, Mohammed, Panahi, Boag, Bennaceur, Sopova, Richardson, Stangl, Rech, Rainer, Ramos, Hofmann, Stellos and Spyridopoulos.
Find related publications in this database (Keywords): acute myocardial infarction; CX3CR1; cytomegalovirus; cardiac MRI; remodeling; T-lymphocytes