Holger Lörchner1, Christian Widera2, Yunlong Hou3, Albrecht Elsässer4, Henning Warnecke5, Evangelos Giannitsis6, Jean-Sebastien Hulot7, Thomas Braun8, Kai C Wollert9, Jochen Pöling10. 1. Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Rhein-Main, Frankfurt am Main, Germany. 2. Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany; Department of Cardiology und Angiology, Hannover Medical School, Hannover, Germany; Department of Cardiology, Heart Center Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany. 3. Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. 4. Department of Cardiology, Heart Center Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany. 5. Department of Cardiac Surgery, Schüchtermann-Clinic, Bad Rothenfelde, Germany; Faculty of Health, Witten/Herdecke University, Witten, Germany. 6. Department of Medicine III, University of Heidelberg, Heidelberg, Germany. 7. Institut National de la Santé et de la Recherche Médicale (INSERM), U970, Paris, France; Cardiovascular Research Center (PARCC), Université Paris Descartes, Paris, France. 8. Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. Electronic address: thomas.braun@mpi-bn.mpg.de. 9. Division of Molecular and Translational Cardiology, Hannover Medical School, Hannover, Germany; Department of Cardiology und Angiology, Hannover Medical School, Hannover, Germany. Electronic address: Wollert.Kai@mh-hannover.de. 10. Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; Department of Cardiac Surgery, Schüchtermann-Clinic, Bad Rothenfelde, Germany. Electronic address: jochen.poeling@mpi-bn.mpg.de.
Abstract
BACKGROUND: Regenerating islet-derived protein 3 beta (Reg3β) is a cardiomyocyte-derived chemokine for macrophages that is upregulated after myocardial infarction (MI) in mice. Here, we hypothesized that monitoring Reg3β expression might provide specific information on the degree of cardiac inflammation, which is a key determinant in disease progression and prognosis of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The expression of Reg3β and other inflammatory markers including C-reactive protein (CRP) and myeloperoxidase (MPO) was measured by immunoblotting at serial time points in the hearts and serum of mice with acute MI. We identified a rapid increase of Reg3β, CRP and MPO expression in cardiac tissue and serum within the first 24 h after MI. The expression of Reg3β peaked at day 4 and thereby paralleled the kinetic profile of the early immune-inflammatory response at sites of cardiac injury, which has been characterized by multicolor flow cytometry. In a retrospective analysis including 322 ACS patients and 117 apparently healthy individuals, we detected increased Reg3β serum concentrations in ACS patients on admission by ELISA. Multiple regression analysis revealed significant relationships between Reg3β and hs-CRP, age, diabetes and NT-proBNP in ACS. Moreover, elevated Reg3β levels on admission were associated with an increased risk of death independent of cardiovascular risk factors and hs-CRP. CONCLUSIONS: Reg3β is a prognostic biomarker for ACS and is strongly associated with the intensity of cardiac inflammation. Accordingly, Reg3β may complement established strategies of acute risk assessment in the management of ACS.
BACKGROUND:Regenerating islet-derived protein 3 beta (Reg3β) is a cardiomyocyte-derived chemokine for macrophages that is upregulated after myocardial infarction (MI) in mice. Here, we hypothesized that monitoring Reg3β expression might provide specific information on the degree of cardiac inflammation, which is a key determinant in disease progression and prognosis of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The expression of Reg3β and other inflammatory markers including C-reactive protein (CRP) and myeloperoxidase (MPO) was measured by immunoblotting at serial time points in the hearts and serum of mice with acute MI. We identified a rapid increase of Reg3β, CRP and MPO expression in cardiac tissue and serum within the first 24 h after MI. The expression of Reg3β peaked at day 4 and thereby paralleled the kinetic profile of the early immune-inflammatory response at sites of cardiac injury, which has been characterized by multicolor flow cytometry. In a retrospective analysis including 322 ACS patients and 117 apparently healthy individuals, we detected increased Reg3β serum concentrations in ACS patients on admission by ELISA. Multiple regression analysis revealed significant relationships between Reg3β and hs-CRP, age, diabetes and NT-proBNP in ACS. Moreover, elevated Reg3β levels on admission were associated with an increased risk of death independent of cardiovascular risk factors and hs-CRP. CONCLUSIONS: Reg3β is a prognostic biomarker for ACS and is strongly associated with the intensity of cardiac inflammation. Accordingly, Reg3β may complement established strategies of acute risk assessment in the management of ACS.
Authors: Claudia C Preston; Tricia D Larsen; Julie A Eclov; Eli J Louwagie; Tyler C T Gandy; Randolph S Faustino; Michelle L Baack Journal: Front Endocrinol (Lausanne) Date: 2020-09-17 Impact factor: 5.555