title: Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease.
abstract: OBJECTIVE
  Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients.
  
  
  RESULTS
  Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden.
  
  
  CONCLUSIONS
  These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Iris I
authors.initials: II
authors.lastname: Müller
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Karin A L
authors.initials: KA
authors.lastname: Müller
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karathanos
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schönleber
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schmid
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Haas
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Tübingen, Tübingen, Germany; Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany. Electronic address: meinrad.gawaz@med.uni-tuebingen.de.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D050197:Atherosclerosis; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D003328:Coronary Thrombosis / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000097:blood* / Q000235:genetics; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000473:pathology; D055815:Young Adult
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Acute coronary syndrome; Coronary artery disease; Grem1; MIF