title: Regulation of microRNA-155 in atherosclerotic inflammatory responses by targeting MAP3K10.
abstract: OBJECTIVE
  Accumulating evidence suggest that numerous microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and differentiation, as well as various diseases that accompany inflammatory responses. Inflammation is known to be a major contributor to atherogenesis. Previous studies provide promising evidence in support of the role of miRNAs in cardiovascular disease. However, mechanistic data on these small molecules in atherosclerosis (AS) are still missing. The present study aims to investigate the potential role of miRNAs in AS.
  
  
  RESULTS
  The miRNA transcriptase was verified by TaqMan real-time polymerase chain reaction assay. Thoracic aorta samples were obtained from Apolipoprotein E knockout mice, and plasma samples were from coronary artery disease (CAD) patients. The results showed that the miR-155 level was the most significantly elevated both in AS mice and CAD patients relative to the normal control. The functional role of miR-155 in the atherosclerotic path physiological process was also observed in vivo and in vitro. The observations suggested that miR-155 is a part of a negative feedback loop, which down-modulates inflammatory cytokine production and decreases AS progression. miR-155 was also found to mediate the inflammatory response and mitogen-activated protein kinase (MAPK) pathway by targeting mitogen-activated protein kinase kinase kinase 10.
  
  
  CONCLUSIONS
  miR-155 contributes to the prevention of AS development and progression. It may also be involved in the posttranscriptional regulation of the inflammatory response and MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Zhoubin
authors.initials: Z
authors.lastname: Li
authors.forename: Mei Mei
authors.initials: MM
authors.lastname: Wong
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zheng
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C099252:oxidized low density lipoprotein; D020930:MAP Kinase Kinase Kinases