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Original research
Elevation of inflammatory S100A8/S100A9 complexes in intracranial aneurysms
  1. Antonius Mattheus de Korte1,
  2. René Aquarius1,
  3. Thomas Vogl2,
  4. Johannes Roth2,
  5. Ronald H M A Bartels1,
  6. Hieronymus D Boogaarts1,
  7. Peter L E M van Lent3,
  8. Joost De Vries1
  1. 1 Department of Neurosurgery, Radboud University Medical Center, Nijmegen, The Netherlands
  2. 2 Institute of Immunology, University of Münster, Munster, Germany
  3. 3 Department of Rheumatology, Radboud University Nijmegen, Nijmegen, The Netherlands
  1. Correspondence to Antonius Mattheus de Korte, Neurosurgery, Radboud University Medical Center, Nijmegen 6500 HB, The Netherlands;{at}


Background Inflammation-related factors might give further insight into the pathophysiology of vessel wall inflammation and intracranial aneurysm (IA) rupture. One of these factors is the protein complex S100A8/A9, which is released by neutrophils, monocytes, and activated macrophages and is known for its role in cardiovascular disease.

Objective To determine if venous S100A8/A9 levels in patients with a ruptured IA (rIA) or unruptured IA (uIA) are elevated compared with a control group. Second, to assess differences between venous and intra-aneurysmal S100A8/A9 levels of rIA and uIA patients.

Methods A prospective case study was performed between June 2016 and May 2017 in patients harboring a ruptured or unruptured saccular IA. Primary outcome measures were individual S100A8/A9 serum concentrations as measured in venous and intra-aneurysmal blood samples during endovascular treatment. Venous serum S100A8/A9 concentrations from a healthy control group served as a reference.

Results We included 16 patients with either a rIA or uIA and 47 healthy controls. Venous S100A8/A9 concentrations were higher in aneurysm patients (rIA and uIA) than those of healthy controls (P≤0.001). S100A8/A9 concentrations were higher in intra-aneurysmal samples than in venous samples of rIA patients (P=0.011). This difference was not found in uIA patients (P=0.054). Intra-aneurysmal S100A8/A9 levels were higher in rIAs than in uIAs (P=0.04).

Conclusions Venous S100A8/A9 levels are elevated in patients with both rIAs and uIAs compared with healthy controls and likely represents aneurysm wall inflammation. S100A8/A9 causes macrophage-induced inflammation and degeneration of the vessel wall which might explain higher intra-aneurysmal S100A8/A9 levels found in rIAs than in uIAs.

  • aneurysm
  • inflammatory response
  • vessel wall

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  • Contributors AMdK, RA, JDV, PLEMvL, HDB, RHMAB: conception, design. AMdK, JDV, RHMAA, HDB, PLEMvL, TV, JR: data acquisition, data analysis. AMdK, RA: drafting the manuscript. JDV, TV, JR, RHMAB, HD, PLEMvL, JDV: revising the manuscript. AMdK, RA, TV, JR, RHMAB, HD, PLEMvL, JV final approval of the submitted manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests Joost de Vries and Hieronymus D. Boogaarts are consultants for Stryker Neurovascular.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.