title: Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms.
abstract: BACKGROUND
  Size and morphological features are associated with intracranial aneurysm (IA) rupture. The cellular mechanisms of IA development and rupture are poorly known.
  
  
  OBJECTIVE
  We studied the expression and phosphorylation of different intracellular signaling molecules in the IA wall compared with IA morphological features to understand better the cellular pathways involved in IA development and wall degeneration.
  
  
  METHODS
  Nine ruptured and 17 unruptured human IA samples were collected intraoperatively. The expression levels and phosphorylation state of 3 mitogen-activated protein kinases (c-Jun N-terminal kinase [JNK], p38, extracellular signal-regulated kinase [ERK]), Bcl-2 antagonist of cell death (Bad), mammalian target of rapamycin (mTOR), cyclic AMP response element binding protein (CREB), and Akt were determined by Western blotting. The localization of signaling proteins was determined by immunofluorescence. From 3-dimensional segmentation of computed tomography angiographic data, size and shape indexes were calculated.
  
  
  RESULTS
  We found a 5-fold difference in phospho-Bad levels between ruptured and unruptured IAs. Phospho-mTOR was downregulated 2.5-fold in ruptured IAs. Phospho-p54 JNK, phospho-p38, and phospho-Akt levels correlated positively with IA size. Phospho-CREB levels were significantly associated with nonsphericity and ellipticity indexes. Phospho-Akt and phospho-p38 correlated negatively with undulation index.
  
  
  CONCLUSIONS
  The signaling pathway profile (apoptosis, cell proliferation, stress signaling) differs between ruptured and unruptured IAs and is associated with IA geometry. Our results increase the knowledge of IA development and wall degeneration.
authors.affiliation: Neurosurgery Research Group, Biomedicum, Helsinki, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Laaksamo
authors.forename: Manasi
authors.initials: M
authors.lastname: Ramachandran
authors.forename: Juhana
authors.initials: J
authors.lastname: Frösen
authors.forename: Riikka
authors.initials: R
authors.lastname: Tulamo
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friedlander
authors.forename: Robert E
authors.initials: RE
authors.lastname: Harbaugh
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Mika
authors.initials: M
authors.lastname: Niemelä
authors.forename: Madhavan L
authors.initials: ML
authors.lastname: Raghavan
authors.forename: Aki
authors.initials: A
authors.lastname: Laakso
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D002532:Intracranial Aneurysm / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*