A central role of plasmin in cardiac injury initiated by fetal exposure to maternal anti-Ro autoantibodies

Paraskevi Briassouli, Marc K Halushka, Joanne H. Reed, Yair Molad, Karen Fox-Talbot, Lucas Buyon, Edwin Guzman, Achiau Ludomirsky, Robert M. Clancy, Jill P. Buyon

Research output: Contribution to journalArticle

Abstract

Objective. Cardiac neonatal lupus (cardiac-NL), initiated by surface binding of anti-Ro60 autoantibodies to apoptotic cardiocytes during development, activates the urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) system. Subsequent accumulation of apoptotic cells and plasmin generation facilitates increased binding of anti-Ro60 by disrupting and cleaving circulating β2-glycoprotein I (β2GPI) thereby eliminating its protective effect. The association of soluble levels of components of the uPA/uPAR system with cardiac-NL was examined. Methods. Levels of the uPA/uPAR system were assessed by ELISA in cord blood and immunohistological evaluation of autopsies. Results. uPA, uPAR and plasminogen levels were each significantly higher in cord blood from cardiac-NL (n = 35) compared with non-cardiac-NL (n = 26) anti-Ro-exposed neonates: 3.3 ± 0.1 vs 1.9 ± 0.05 ng/ml (P

Original languageEnglish (US)
Article numberket156
Pages (from-to)1448-1453
Number of pages6
JournalRheumatology
Volume52
Issue number8
DOIs
Publication statusPublished - Aug 2013

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Keywords

  • Apoptosis
  • Fibrosis
  • Inflammation

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Briassouli, P., Halushka, M. K., Reed, J. H., Molad, Y., Fox-Talbot, K., Buyon, L., ... Buyon, J. P. (2013). A central role of plasmin in cardiac injury initiated by fetal exposure to maternal anti-Ro autoantibodies. Rheumatology, 52(8), 1448-1453. [ket156]. https://doi.org/10.1093/rheumatology/ket156