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Antioxid Redox Signal. 2015 Oct 10;23(11):865-79. doi: 10.1089/ars.2014.6243. Epub 2015 Aug 11.

Interaction of MIF Family Proteins in Myocardial Ischemia/Reperfusion Damage and Their Influence on Clinical Outcome of Cardiac Surgery Patients.

Author information

1
1 Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University , Aachen, Germany .
2
2 Department of Anesthesiology, University Hospital, RWTH Aachen University , Aachen, Germany .
3
3 Department of Anesthesiology, University Hospitals Leuven , Leuven, Belgium .
4
4 Department of Cardiovascular Sciences, University of Leuven , Leuven, Belgium .
5
5 Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen University , Aachen, Germany .
6
6 Department of Burn Surgery, Shanghai Hospital, Second Military Medical University , Changhai, People's Republic of China .
7
7 Department of Medicine, Yale University School of Medicine , New Haven, Connecticut.
8
8 Department of Pharmacology, Yale University School of Medicine , New Haven, Connecticut.
9
9 Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich , Munich, Germany .
10
10 German Center for Cardiovascular Research (DZHK), Munich Heart Alliance , Munich, Germany .
11
11 August-Lenz-Stiftung, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich , Munich, Germany .

Abstract

AIMS:

Cardiac surgery involves myocardial ischemia/reperfusion (I/R) with potentially deleterious consequences. Macrophage migration inhibitory factor (MIF) is a stress-regulating chemokine-like cytokine that protects against I/R damage, but functional links with its homolog, d-dopachrome tautomerase (MIF-2), and the circulating soluble receptor CD74 (sCD74) are unknown. In this study, we investigate the role of MIF, MIF-2, sCD74, and MIF genotypes in patients scheduled for elective single or complex surgical procedures such as coronary artery bypass grafting or valve replacement.

RESULTS:

MIF and MIF-2 levels significantly increased intraoperatively, whereas measured sCD74 decreased correspondingly. Circulating sCD74/MIF complexes were detectable in 50% of patients and enhanced MIF antioxidant activity. Intraoperative MIF levels were independently associated with a reduced risk for the development of atrial fibrillation (AF) (odds ratio 0.99 [0.98-1.00]; p=0.007). Circulating levels of MIF-2, but not MIF, were associated with an increased frequency of organ dysfunction and predicted the occurrence of AF (area under the curve [AUC]=0.663; p=0.041) and pneumonia (AUC=0.708; p=0.040). Patients with a high-expression MIF genotype exhibited a reduced incidence of organ dysfunction compared with patients with low-expression MIF genotypes (3 vs. 25; p=0.042).

INNOVATION:

The current study comprehensively highlights the kinetics and clinical relevance of MIF family proteins and the MIF genotype in cardiac surgery patients.

CONCLUSION:

Our findings suggest that increased MIF levels during cardiac surgery feature organ-protective properties during myocardial I/R, while the soluble MIF receptor, sCD74, may enhance MIF antioxidant activity. In contrast, high MIF-2 levels are predictive of the development of organ dysfunction. Importantly, we provide first evidence for a gene-phenotype relationship between variant MIF alleles and clinical outcome in cardiac surgery patients.

PMID:
26234719
PMCID:
PMC4615780
DOI:
10.1089/ars.2014.6243
[Indexed for MEDLINE]
Free PMC Article

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