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

Abstract

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
JournalBiomedicines
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Apr 2023

Keywords

  • proteoglycan
  • extracellular matrix
  • biomarker
  • heart failure
  • fibrosis
  • immunotherapy
  • MYOCARDIAL-INFARCTION
  • SERUM SYNDECAN-4
  • FAILURE
  • EXPRESSION
  • PROTEOGLYCANS
  • ASSOCIATION
  • DYSFUNCTION
  • BIOMARKER

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