Hilde L Orrem1, Christian Shetelig2, Thor Ueland3, Shanmuganathan Limalanathan4, Per H Nilsson5, Trygve Husebye6, Pål Aukrust7, Ingebjørg Seljeflot8, Pavel Hoffmann9, Jan Eritsland10, Tom E Mollnes11, Geir Øystein Andersen12, Arne Yndestad13. 1. Department of Immunology, Oslo University Hospital Rikshospitalet, Norway; Department of Anesthesiology, Oslo University Hospital Rikshospitalet, Norway; Institute of Clinical Medicine, University of Oslo, Norway. 2. Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway. 3. Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway. 4. Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway; Feiring Heart Clinic, Feiring, Norway. 5. K.G. Jebsen Inflammatory Research Centre, University of Oslo, Norway; Linnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden. 6. Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center of Heart Failure Research, University of Oslo, Norway. 7. Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; K.G. Jebsen Inflammatory Research Centre, University of Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway. 8. Institute of Clinical Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway; Center of Heart Failure Research, University of Oslo, Norway. 9. Institute of Clinical Medicine, University of Oslo, Norway; Section of Interventional Cardiology, Oslo University Hospital Ullevål, Norway. 10. Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway. 11. Department of Immunology, Oslo University Hospital Rikshospitalet, Norway; K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway; K.G. Jebsen Inflammatory Research Centre, University of Oslo, Norway; Research Laboratory, Nordland Hospital, Bodø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science, Trondheim, Norway. 12. Department of Cardiology, Oslo University Hospital Ullevål, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Norway; Center of Heart Failure Research, University of Oslo, Norway. 13. Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway; K.G. Jebsen Inflammatory Research Centre, University of Oslo, Norway; Center of Heart Failure Research, University of Oslo, Norway. Electronic address: arne.yndestad@medisin.uio.no.
Abstract
BACKGROUND: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1α and IL-1β are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. METHODS: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65). RESULTS: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. CONCLUSION: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI.
BACKGROUND: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1α and IL-1β are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. METHODS: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65). RESULTS:IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. CONCLUSION: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI.
Authors: Maria E R Coste; Carolina N França; Maria Cristina Izar; Daniela Teixeira; Mayari E Ishimura; Ieda Longo-Maugeri; Amanda S Bacchin; Henrique Tria Bianco; Flavio T Moreira; Ibraim Masciarelli Pinto; Gilberto Szarf; Adriano Mendes Caixeta; Otavio Berwanger; Iran Gonçalves; Francisco A H Fonseca Journal: Arq Bras Cardiol Date: 2020-12 Impact factor: 2.000