Inflammation and Syndecan-4 Shedding from Cardiac Cells in Ischemic and Non-Ischemic Heart Disease

M.E. Strand, M. Vanhaverbeke, M.T.H.M. Henkens, M.A. Sikking, K.B. Rypdal*, B. Braathen, V.M. Almaas, T. Tonnessen, G. Christensen, S. Heymans, I.G. Lunde

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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)-1 beta and its inhibitor IL-1 receptor antagonist (IL-1Ra), or tumor necrosis factor (TNF)alpha 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-1 beta-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.
Original languageEnglish
Article number1066
Number of pages17
Issue number4
Publication statusPublished - 1 Apr 2023


  • proteoglycan
  • extracellular matrix
  • biomarker
  • heart failure
  • fibrosis
  • immunotherapy


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