Elevation of inflammatory S100A8/S100A9 complexes in intracranial aneurysms

J Neurointerv Surg. 2020 Nov;12(11):1117-1121. doi: 10.1136/neurintsurg-2019-015753. Epub 2020 Apr 24.


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.

Keywords: aneurysm; inflammatory response; vessel wall.

MeSH terms

  • Adult
  • Aged
  • Aneurysm, Ruptured / blood*
  • Aneurysm, Ruptured / diagnosis
  • Biomarkers / blood
  • Calgranulin A / blood*
  • Calgranulin B / blood*
  • Cohort Studies
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Intracranial Aneurysm / blood*
  • Intracranial Aneurysm / diagnosis
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Neutrophils / metabolism
  • Prospective Studies
  • Young Adult


  • Biomarkers
  • Calgranulin A
  • Calgranulin B
  • Inflammation Mediators
  • S100A8 protein, human
  • S100A9 protein, human