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The Fractalkine Receptor CX 3 CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling
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The Fractalkine Receptor CX 3 CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling
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Journal Article
The Fractalkine Receptor CX 3 CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling
2021
Overview
Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX
CR1
effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX
CR1 (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 CX
CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX
CR1
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 CX
CR1
T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.
Subject
/ CX3C Chemokine Receptor 1 - genetics
/ CX3C Chemokine Receptor 1 - metabolism
/ Cytomegalovirus Infections - complications
/ Cytomegalovirus Infections - virology
/ Female
/ Humans
/ Male
/ Myocardial Infarction - complications
/ Myocardial Infarction - diagnosis
/ Myocardial Infarction - metabolism
/ Myocardial Infarction - mortality
/ Receptors, CCR7 - metabolism
