Iris I Müller1, Karin A L Müller1, Athanasios Karathanos1, Heiko Schönleber1, Dominik Rath1, Sebastian Vogel1, Madhumita Chatterjee1, Martina Schmid1, Maximilian Haas1, Peter Seizer1, Harald Langer1, Elke Schaeffeler2, Matthias Schwab3, Meinrad Gawaz4, Tobias Geisler5. 1. Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany. 2. Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. 3. Department of Clinical Pharmacology, University Hospital of Tübingen, Tübingen, Germany; Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. 4. Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany. Electronic address: meinrad.gawaz@med.uni-tuebingen.de. 5. Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Hospital of Tübingen, Tübingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
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. METHODS AND 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. CONCLUSION: 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.
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 cardiovascularpatients. METHODS AND 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. CONCLUSION: 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: Corinna Schmitz; Heidi Noels; Omar El Bounkari; Eva Straussfeld; Remco T A Megens; Marieke Sternkopf; Setareh Alampour-Rajabi; Christine Krammer; Pathricia V Tilstam; Norbert Gerdes; Christina Bürger; Aphrodite Kapurniotu; Richard Bucala; Joachim Jankowski; Christian Weber; Jürgen Bernhagen Journal: FASEB J Date: 2018-03-15 Impact factor: 5.191