Elsevier

Cytokine

Volume 113, January 2019, Pages 365-370
Cytokine

Prognostic value of fractalkine/CX3CL1 concentration in patients with acute myocardial infarction treated with primary percutaneous coronary intervention

https://doi.org/10.1016/j.cyto.2018.10.006Get rights and content

Highlights

  • FKN involves in the inflammatory and remodeling processes after AMI.

  • FKN is negative correlated with myocardial salvage in STEMI patients underwent PCI.

  • Higher FKN level after primary PCI predicts worse MACE events in AMI patients.

Abstract

Background

Recent studies demonstrated that fractalkine (FKN) is critically involved in the regulation of inflammation and cardiac function.

Objective

This study aimed to investigate the prognostic value of circulating FKN in patients with ST-elevated acute myocardial infarction (STEMI) after primary PCI.

Methods

We enrolled ninety consecutive STEMI patients and investigated the association of circulating FKN with myocardial salvage and the occurrence of major adverse cardiac events (MACE) after PCI.

Results

During a median follow-up of 387 days, total 15 MACE (16.67%) were registered in the study population. Patients with MACE were more likely to be occurred in elderly patients with 3-vessel disease. Correlation analysis demonstrated the level of FKN at day 1 after PCI (FKN@day-1) not only significantly correlated with the levels of hs-TnT at day 7 after PCI (R2 = 0.06; p = 0.02) but inversely correlated with the measurements of LVEF at 1-month observation (R2 = 0.10; p = 0.00). Kaplan-Meier survival analyses further revealed that patients with the level of FKN@day-1 above the median had a higher incidence of MACE compared with those whose FKN@day-1 levels below the median (log-rank test x2 = 13.29, p < 0.001). In addition, multivariate Cox regression analysis demonstrated that FKN@day-1 was an independent predictor of MACE (hazard ratio: 4.63; 95% confidence interval: 1.53–14.01; p = 0.00), together with WBC count and 3-vessel disease for STEMI patients.

Conclusions

Our study demonstrates that FKN@day-1 is negative correlated with myocardial salvage after acute myocardial infarction and might be a valuable prognostic marker of MACE in patients with STEMI undergone PCI.

Introduction

Although the mechanisms leading to myocardial injury and repairment after acute myocardial infarction (AMI) remain incompletely understood, research has shown that inflammation and immune cells paly a key role in this pathophysiological process [1], [2], [3], [4], [5], [6]. Of which the chemokine family is particularly important and of interest [1], [5], [7]. It has been reported that chemokines can regulate the infiltration of inflammatory cells, including T cells, B cells, monocytes/macrophages, and dendritic cells to the injury sites right after the onset of AMI [8]. Chemokines also a strong inducer for the proliferation of T cells and B cells, as well as promoting the production mass of cytokines and other chemokines to amplify the inflammation, aggravate the tissue damage or even enhance angiogenesis [1], [9], [10], [11]. Therefore, chemokines may be important players in the pathogenesis of AMI, and blocking the certain actions of chemokines could be a novel approach for reverse the pathological remodeling after AMI.

Fractalkine/CX3CL1 (FKN) is a recently discovered chemokine. It has two forms: the membrane-anchored and the free soluble form (sFKN). The membrane-anchored FKN is expressed primarily on the surface of activated endothelial, smooth muscle cells, anchoring the circulating monocytes and T cells to the injury site [12]. Meanwhile, the sFKN act as a chemotactic stimulus, which strongly induces the production of inflammation cells [13], [14]. Studies have shown that the level of sFKN is increased in unstable coronary artery disease, and may be related to plaque rupture [14], [15], [16]. In addition, it has been shown that both myocardial and soluble FKN are increased in heart failure and could be a valuable prognostic biomarker for chronic heart failure [17], [18]. Although sFKN is reported to involve in myocardial inschemia/reperfusion injury of AMI patients and can be a risk factor for cardiovascular disease (CVD) [19], little is known about the relationship between the sFKN and the subsequent cardiac function and outcomes in AMI patients.

In the present study, we aimed to investigate the levels of sFKN and evaluate its prognostic values in AMI patients who underwent primary percutaneous coronary intervention (pPCI).

Section snippets

Patients population

The study protocol had been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and was approved by the institutional ethics committee of Northern Jiangsu province hospital and clinical medical college of Yangzhou University (2016KY-186). The informed consent was obtained from either the patients or their family members. We recruited ninety consecutive STEMI patients admitted to the hospital between September 2016 and April

Patient characteristics

Characteristics of the study population are shown in Table 1. Ninety STEMI patients (70 men, 77.78%) on hospital admission were eligible for this study. Mean age of the patients was 63.93 ± 11.94 years. The symptom-to-balloon time (time from symptom onset to receiving balloon dilation treatment) was 7.36 ± 5.69 h. On admission, all patients had elevated hs-TnT (normal upper limitation, 0.014 μg/L). The patients were then divided into 2 groups according to the occurrence of MACE events or not

Discussion

In the present study we investigated the association between the circulating FKN and the clinical outcomes of STEMI patients after primary PCI. There are 2 main findings of our study. First, a higher level of FKN after PCI significantly increases the probability of cumulative MACE occurrence during follow-up. Second, this biomarker positively correlated with the level of cardiac Troponin T and predicts the cardiac function after AMI. To our best knowledge, no previous studies have examined FKN

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC 81570328, Wang Junhong), the “Sixth-Peak Talent” of Jiangsu Province (2013WSN-036, Wang Junhong) and Jiangsu Provincial Commission of Health and Family Planning (Z2017010, Xu Bing) and Dr. Wang Junhong was also support by the Jiangsu Province’s Key Provincial Talents Program (ZDRCB2016005).

Conflict of interest

The authors have declared that no conflict of interest exists.

References (28)

  • R. Altara et al.

    Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases

    Clin. Sci. (Lond).

    (2016)
  • S.E. Boag et al.

    T lymphocytes and fractalkine contribute to myocardial ischemia/reperfusion injury in patients

    J. Clin. Invest.

    (2015)
  • S.E. Boag et al.

    Lymphocyte communication in myocardial ischemia/reperfusion injury

    Antioxid. Redox Signal.

    (2017)
  • L. Chen et al.

    Monocyte chemoattractant protein 1 and fractalkine play opposite roles in angiogenesis via recruitment of different macrophage subtypes

    Int. J. Ophthalmol.

    (2018)
  • Cited by (0)

    1

    These authors contributed equally to this work.

    View full text