title: Integrated analysis of microarray data of atherosclerotic plaques: modulation of the ubiquitin-proteasome system.
abstract: Atherosclerosis is a typical complex multi-factorial disease and many molecules at different levels and pathways were involved in its development. Some studies have investigated the dysregulation in atherosclerosis at mRNA, miRNA or DNA methylation level, respectively. However, to our knowledge, the studies that integrated these data and revealed the abnormal networks of atherosclerosis have not been reported. Using microarray technology, we analyzed the omics data in atherosclerosis at mRNA, miRNA and DNA methylation levels. Our results demonstrated that the global DNA methylation and expression of miRNA/mRNA were significantly decreased in atherosclerotic plaque than in normal vascular tissue. The interaction network constructed using the integrative data revealed many genes, cellular processes and signaling pathways which were widely considered to play crucial roles in atherosclerosis and also revealed some genes, miRNAs or signaling pathways which have not been investigated in atherosclerosis until now (e.g. miR-519d and SNTB2). Moreover, the overall protein ubiquitination in atherosclerotic plaque was significantly increased. The proteasome activity was increased early but decreased in advanced atherosclerosis. Our study revealed many classic and novel genes and miRNAs involved in atherosclerosis and indicated the effects of ubiquitin-proteasome system on atherosclerosis might be closely related to the course of atherosclerosis. However, the efficacy of proteasome inhibitors in the treatment of atherosclerosis still needs more research.
authors.affiliation: Division of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurology, Liaocheng People's Hospital, Medical School of Liaocheng, Taishan Medical University, Liaocheng, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.affiliation: School of Information Science and Engineering, Zaozhuang University, Zaozhuang, Shandong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Shanghai University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Qunye
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D059372:Nucleotide Motifs; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D056510:Position-Specific Scoring Matrices; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex