Inflammation and Syndecan-4 Shedding from Cardiac Cells in Ischemic and Non-Ischemic Heart Disease
Autor: | Mari E. Strand, Maarten Vanhaverbeke, Michiel T. H. M. Henkens, Maurits A. Sikking, Karoline B. Rypdal, Bjørn Braathen, Vibeke M. Almaas, Theis Tønnessen, Geir Christensen, Stephane Heymans, Ida G. Lunde |
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Přispěvatelé: | MUMC+: DA Pat AIOS (9), MUMC+: DA Pat Toegelatenen (9), Cardiologie, RS: Carim - B03 Cell biochemistry of thrombosis and haemostasis, RS: Carim - H02 Cardiomyopathy |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Biomedicines, 11(4):1066. MDPI AG Biomedicines; Volume 11; Issue 4; Pages: 1066 |
ISSN: | 2227-9059 |
Popis: | Circulating biomarkers reflecting cardiac inflammation are needed to improve the diagnostics and guide the treatment of heart failure patients. The cardiac production and shedding of the transmembrane proteoglycan syndecan-4 is upregulated by innate immunity signaling pathways. Here, we investigated the potential of syndecan-4 as a blood biomarker of cardiac inflammation. Serum syndecan-4 was measured in patients with (i) non-ischemic, non-valvular dilated cardiomyopathy (DCM), with (n = 71) or without (n = 318) chronic inflammation; (ii) acute myocarditis (n = 15), acute pericarditis (n = 3) or acute perimyocarditis (23) and (iii) acute myocardial infarction (MI) at day 0, 3 and 30 (n = 119). Syndecan-4 was investigated in cultured cardiac myocytes and fibroblasts (n = 6–12) treated with the pro-inflammatory cytokines interleukin (IL)-1β and its inhibitor IL-1 receptor antagonist (IL-1Ra), or tumor necrosis factor (TNF)α and its specific inhibitor infliximab, an antibody used in treatment of autoimmune diseases. The levels of serum syndecan-4 were comparable in all subgroups of patients with chronic or acute cardiomyopathy, independent of inflammation. Post-MI, syndecan-4 levels were increased at day 3 and 30 vs. day 0. IL-1Ra attenuated IL-1β-induced syndecan-4 production and shedding in vitro, while infliximab had no effect. In conclusion, syndecan-4 shedding from cardiac myocytes and fibroblasts was attenuated by immunomodulatory therapy. Although its circulating levels were increased post-MI, syndecan-4 did not reflect cardiac inflammatory status in patients with heart disease. |
Databáze: | OpenAIRE |
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