title: Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods.
abstract: Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the "immune response" and "muscle contraction" were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the "FcεRI-mediated signaling pathway", while down-regulated genes were significantly enriched in the "transforming growth factor-β signaling pathway". Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Nai
authors.affiliation: Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Diane
authors.initials: D
authors.lastname: Threapleton
authors.affiliation: Department of Vascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Vascular Surgery, People's hospital of Henan province, Zhengzhou university, Zhengzhou 450003, Henan, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: You
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Zejin
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Health Management, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060833:Cellular Microenvironment / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020411:Oligonucleotide Array Sequence Analysis; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025941:Protein Interaction Mapping; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics* / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6