title: Comparative proteome analysis of saccular intracranial aneurysms with iTRAQ quantitative proteomics.
abstract: OBJECTIVE
  To screen differentially expressed proteins of saccular intracranial aneurysms and superficial temporal artery by the proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) combined with reverse phase high-performance liquid chromatography.
  
  
  METHODS
  Collecting 17 samples from intracranial aneurysm patients undergoing aneurysmectomy as experiment group and 17 matched STA as control group. After quantification and enzymolysis of the protein, the iTRAQ were used to label the peptides of the 2 groups respectively. Then, the mixture of the peptides was fractioned by RP-HPLC and analyzed by LC-MS/MS to identify the differential expression proteins.
  
  
  RESULTS
  A total of 1699 proteins were identified from the ProteinPilot 4.5 software (AB SCIEX) using the Paragon database search algorithm. Comparing with STA, 54 proteins were significantly up-regulated (115:114<0.5-fold) and 37 were significantly down-regulated in sIAs (115:114>2.0-fold). Furthermore, Integrin β3, Secreted frizzled-related protein 2 were significantly up-regulated (2.3 fold and 2.1 fold, respectively), whereas MyosinIIb, Alpha-actinin-1, Laminin β2, and Carboxypeptidase A3 were down-regulated (3.01 fold, 2.1 fold, 2.07 fold, and 2.01 fold, respectively) in sIAs. GO Ontology analysis showed that most differential proteins expressed in cytoskeletal; up-regulated proteins in sIAs play an important role in inflammatory reaction, enzymatic hydrolysis, cell adhesion and invasion, and cellular immune reaction; down-regulated proteins in sIAs involved in cytoskeletal protein, enzyme, and structural protein. ITGB3, ACTN1 and MYL2 play a role in aneurysm formation via focal adhesion pathway. The results of Western-blot assay were consistent with the proteomic changes of those 6 proteins.
  
  
  CONCLUSIONS
  The differentially expressed proteins in sIAs that showed aneurysm formation are related to cytoskeleton abnormal and extracellular matrix changes. The iTRAQ technology provides scientific foundation for the further study to explore the pathogenic mechanism of sIAs.
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
authors.forename: Lanbing
authors.initials: L
authors.lastname: Yu
authors.affiliation: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China.
authors.forename: Xiahe
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, China. Electronic address: zhaojz205@gmail.com.
authors.forename: Jizong
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D003599:Cytoskeleton / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D002532:Intracranial Aneurysm / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D025941:Protein Interaction Mapping; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D004798:Enzymes; D020543:Proteome
keywords: Alpha-actinin-1; Carboxypeptidase A3; ITRAQ; Integrin beta3; Laminin B2; MyosinIIb; Saccular intracranial aneurysms; Secreted frizzled-related protein 2