C4b-Binding Protein Deposition is Induced in Diseased Aortic Heart Valves, Coinciding with C3d

M.J. Dikhoff, M. ter Weeme, A.B.A. Vonk, K. Kupreishvili, A.M. Blom, P.A.J. Krijnen, W. Stooker, H.W.M. Niessen

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BACKGROUND AND AIM OF THE STUDY: It has been found recently that activated complement is more widespread in diseased aortic valves compared to the endogenous complement inhibitors C1-inhibitor and clusterin. Previously, another endogenous inhibitor of complement, C4b-binding protein (C4BP) has been described in atherosclerotic diseased coronary arteries. The study aim was to analyze C4BP levels in diseased aortic valves.

METHODS: Aortic valve tissue was derived from surgical procedures and classified as 'degenerative', 'atherosclerotic' or 'atherosclerotic with bacterial infection'. Valves were stained with specific antibodies against C4BP, C3d and caspase-3. Areas of positivity were then quantified using computer- assisted morphometry.

RESULTS: In atherosclerotic valves, the areas of C4BP and C3d positivity (38.8 +/- 0.4% versus 32.7 +/- 1.0%, respectively) were significantly higher compared to the degenerative and control groups. In atherosclerotic valves with bacterial infection, the area of positivity for C4BP was even further increased compared to atherosclerotic valves (65.1 +/- 1.2%; 70.1 +/- 1.9% for C3d). The areas of C4BP and C3d positivity were not significantly different in all groups. Caspase-3 was only present in <10% of endothelial cells in the atherosclerotic valves without bacterial infection and in neutrophilic granulocytes in atherosclerotic valves, with and without bacterial infection.

CONCLUSION: It has been shown for the first time that C4BP is deposited in the diseased aortic valve, coinciding with C3d. The area of C4BP positivity was more extensive compared to the areas of other endogenous complement inhibitors (C1-inhibitor and clusterin).

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalJournal of heart valve disease
Issue number4
Publication statusPublished - 2015


  • Adult
  • Aged
  • Aged, 80 and over
  • Aortic Valve
  • Case-Control Studies
  • Caspase 3
  • Complement C3d
  • Complement C4b-Binding Protein
  • Female
  • Heart Valve Diseases
  • Humans
  • Image Interpretation, Computer-Assisted
  • Immunohistochemistry
  • Journal Article
  • Male
  • Middle Aged
  • Research Support, Non-U.S. Gov't

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