title: MicroRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1α in the progression of atherosclerosis.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a master regulator of cellular energy metabolism that is associated with many cardiovascular diseases, including atherosclerosis. However, the role and underling regulatory mechanisms of PGC-1α in the pathogenesis of atherosclerosis are not completely understood. Here, we identified the microRNAs that post-transcriptionally regulate PGC-1α production and their roles in the pathogenesis of atherosclerosis.
  
  
  RESULTS
  A significant down-regulation of PGC-1α protein was observed in human atherosclerotic vessel samples. Using microarray and bioinformatics analyses, PGC-1α was identified as a common target gene of miR-19b-3p, miR-221-3p and miR-222-3p, which are mainly located in the intima of atherosclerotic vessels. In vitro induction of miR-19b-3p, miR-221-3p and miR-222-3p by the inflammatory cytokines TNFα and IFNγ may affect PGC-1α protein production and consequently result in mitochondrial dysfunction in Human Aortic Endothelial Cells (HAECs). The overexpression of miR-19b-3p, miR-221-3p and miR-222-3p in HAECs caused intracellular ROS accumulation, which led to cellular apoptosis.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate that PGC-1α plays a protective role against the vascular complications of atherosclerosis. Moreover, the posttranscriptional regulation of PGC-1α by miR-19b/221/222 was unveiled, which provides a novel mechanism in which a panel of microRNAs can modulate endothelial cell apoptosis via the regulation mitochondrial function.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Yunxing
authors.initials: Y
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Hanying
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China. Electronic address: jingli220@nju.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
authors.forename: Dongjin
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China. Electronic address: xiaohongjiang@nju.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D001011:Aorta / Q000473:pathology; D017209:Apoptosis; D050197:Atherosclerosis / Q000097:blood*; D019295:Computational Biology; D018450:Disease Progression; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D007371:Interferon-gamma; D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C549214:MIRN19A microRNA, human; C525709:MIR221, human; C525710:MIR222, human; C486497:PPARGC1A protein, human
keywords: Atherosclerosis; PGC-1α; miR-19b-3p; miR-221-3p; miR-222-3p