title: Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable angina.
abstract: BACKGROUND
  Statin therapy plays a pivotal role in stabilizing the plaque for unstable angina (UA) patients although its mechanism(s) remains largely unexplored. Here we aim to identify microRNAs (miRNAs) mediating the protective effect of statins in UA patients.
  
  
  METHODS
  MiRNAs Array was carried out to compare the circulating whole blood miRNA profile of UA patients treated with (n = 10) and without statin (n = 10) and plasma miRNA profile UA patients treated with (n = 5) and without statin (n = 5). 22 whole blood miRNAs and 19 plasma miRNAs were found significantly upregulated in statin group. Targets of these miRNAs were predicted by algoritms: Targetscan, Miranda and Diana microT, then clustered according to functions and cell types by using the Database for Annotation, Visualization and Integrated Discovery (DAVID). To reveal the enriched function pathways in human atherosclerotic plaque, we analyzed microarray data from GEO database, Coronary atherosclerotic plaque (n = 80); macrophages in ruptured plaque (n = 11); carotid atheroma plaque (n = 64); advanced carotid atherosclerotic plaque (n = 29) using Reactome database. Integrated analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion. In vulnerable plaque, additional immune system signaling was also targeted.
  
  
  RESULTS
  The data showed target genes regulated by these statin induced miRNAs majorly expressed in i) plaque macrophage and platelet, where they were involved in hemostasis process; ii) in monocyte to regulate NGF apoptosis; iii) and in endothelial cell function in Rho GTPase pathway. Integrate analysis indicated that statin induced miRNAs mainly regulate the signaling pathways of Rho GTPase and hemostasis in human atherosclerotic lesion.
  
  
  CONCLUSIONS
  Our study suggest that statin induces the expression of multiple miRNAs in the circulation of UA patient, which play important roles by regulating signal pathways critical for the pathogenesis of UA.
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. lijingjin@bjmu.edu.cn.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. chenhongbj@medmail.com.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. renjingyi@pkuph.edu.cn.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. Sjx221@163.com.
authors.forename: Junxian
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. merryfly2002@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. Zhjingpku@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. ayulee9@126.com.
authors.forename: Chongyou
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. lsf@bjmu.edu.cn.
authors.forename: Sufang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. gengqiang0533@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Geng
authors.affiliation: Department of Cardiology, Peking University People's hospital, No. 11 Xizhimen South Street, Beijing, 100044, China. caochengfu85@163.com.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden. ning.xu@ki.se.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
mesh_terms: D000368:Aged; D000465:Algorithms; D000789:Angina, Unstable / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D003331:Coronary Vessels / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006487:Hemostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007107:Immune System; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D035683:MicroRNAs; D020741:rho GTP-Binding Proteins