Journal article
Intracellular Signaling Pathways and Size, Shape, and Rupture History of Human Intracranial Aneurysms
Neurosurgery, Vol.70(6), pp.1565-1573
06/01/2012
DOI: 10.1227/NEU.0b013e31824c057e
PMID: 22278358
Abstract
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. CONCLUSION: 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.
Details
- Title: Subtitle
- Intracellular Signaling Pathways and Size, Shape, and Rupture History of Human Intracranial Aneurysms
- Creators
- Elisa Laaksamo - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, FinlandManasi Ramachandran - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaJuhana Frösen - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland, Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, FinlandRiikka Tulamo - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, FinlandMarc Baumann - Protein Chemistry/Proteomics Laboratory, Institute of Biomedicine, University of Helsinki, Helsinki, FinlandRobert M Friedlander - Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PennsylvaniaRobert E Harbaugh - Department of Neurosurgery, Penn State University College of Medicine, Hershey, PennsylvaniaJuha Hernesniemi - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland, Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, FinlandMika Niemelä - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland, Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, FinlandMadhavan L Raghavan - Department of Biomedical Engineering, University of Iowa, Iowa City, IowaAki Laakso - Neurosurgery Research Group, Biomedicum Helsinki, Helsinki University Central Hospital, Helsinki, Finland, Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
- Resource Type
- Journal article
- Publication Details
- Neurosurgery, Vol.70(6), pp.1565-1573
- DOI
- 10.1227/NEU.0b013e31824c057e
- PMID
- 22278358
- ISSN
- 0148-396X
- eISSN
- 1524-4040
- Language
- English
- Date published
- 06/01/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering
- Record Identifier
- 9984064209802771
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