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Comparative proteome analysis of saccular intracranial aneurysms with iTRAQ quantitative proteomics
Jia Wang1, Lanbing Yu1, Xiahe Huang2
1Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
Journal of Proteomics
|September 20, 2015
Summary
Proteomics analysis revealed significant differences in protein expression between saccular intracranial aneurysms (sIAs) and superficial temporal arteries (STAs). These findings highlight cytoskeleton abnormalities and extracellular matrix changes as key factors in aneurysm formation, paving the way for further research into sIA pathogenesis.
Area of Science:
- Proteomics
- Vascular Biology
- Biochemistry
Background:
- Saccular intracranial aneurysms (sIAs) pose significant health risks.
- Understanding the molecular mechanisms underlying sIA formation is crucial for developing effective treatments.
Purpose of the Study:
- To identify differentially expressed proteins in sIAs compared to superficial temporal artery (STA) using isobaric tags for relative and absolute quantification (iTRAQ) proteomics.
- To investigate the potential role of these proteins in the pathogenesis of sIAs.
Main Methods:
- Proteomic analysis of 17 sIA and 17 STA samples using iTRAQ labeling.
- Peptide fractionation by reverse-phase high-performance liquid chromatography (RP-HPLC) and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Bioinformatic analysis including Gene Ontology (GO) analysis and Western-blot validation.
Main Results:
- A total of 1699 proteins were identified.
- 54 proteins were significantly upregulated and 37 downregulated in sIAs compared to STAs.
- Key proteins like Integrin β3 and Secreted frizzled-related protein 2 were upregulated, while Myosin IIb and Alpha-actinin-1 were downregulated.
- Differentially expressed proteins are associated with cytoskeletal changes, inflammation, cell adhesion, and extracellular matrix remodeling.
- Focal adhesion pathway proteins (ITGB3, ACTN1, MYL2) were implicated in aneurysm formation.
Conclusions:
- Aberrant cytoskeletal structure and extracellular matrix alterations are linked to sIA development.
- iTRAQ-based proteomics provides a foundation for elucidating the pathogenic mechanisms of sIAs.
- The identified proteins represent potential targets for future therapeutic strategies against intracranial aneurysms.
