title: Coactivator-associated arginine methyltransferase 1 targeted by miR-15a regulates inflammation in acute coronary syndrome.
abstract: OBJECTIVE
  Coactivator-associated arginine methyltransferase 1 (CARM1) is essential for the activation of a subset of NF-кB-dependent genes, which code the chemokines triggering plaque vulnerability. Unstable atherosclerotic plaques lead to the onset of acute coronary syndrome (ACS). Therefore, we aimed to investigate whether CARM1 is involved in the pathogenesis of ACS and ascertain the regulatory mechanism of CARM1 expression at posttranscriptional level.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of 19 patients with ACS and 22 subjects with risk factors for coronary heart disease. Gene expression was determined by quantitative real-time PCR and Western blot. The effects of CARM1 and miR-15a on their target genes expression were assessed by gain-of-function and loss-of-function approaches.
  
  
  RESULTS
  PBMCs from patients with ACS showed higher levels of CARM1 mRNA and protein expression. The levels of CARM1 mRNA were positively correlated with three chemokines including interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and interleukin-8 (IL-8) in PBMCs (CARM1 and IP-10: r=0.55, P=0.008; CARM1 and MCP-1: r=0.64, P=0.002; CARM1 and IL-8: r=0.55, P=0.008). Moreover, CARM1 regulated the transcription of these chemokines in human embryonic kidney 293T (HEK293T) cells. We also found that the levels of miR-15a were decreased by 37% in patients with ACS and miR-15a modulated CARM1 expression through targeted binding to CARM1 3'-UTR.
  
  
  CONCLUSIONS
  The present study demonstrated that CARM1 targeted by miR-15a played an important role in chemokine activation in the pathogenesis of ACS.
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Human Genome Center at Beijing, Beijing 100176, China. Electronic address: liuxuehui209@163.com.
authors: Xuehui
authors: X
authors: Liu
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Human Genome Center at Beijing, Beijing 100176, China. Electronic address: wanglaiyuandw@163.com.
authors: Laiyuan
authors: L
authors: Wang
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Human Genome Center at Beijing, Beijing 100176, China. Electronic address: ccmls0965@gmail.com.
authors: Hongfan
authors: H
authors: Li
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China. Electronic address: xiangfenglu@sina.com.
authors: Xiangfeng
authors: X
authors: Lu
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China; National Human Genome Center at Beijing, Beijing 100176, China. Electronic address: huyyg@163.com.
authors: Yongyan
authors: Y
authors: Hu
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China. Electronic address: yangxueli1985@gmail.com.
authors: Xueli
authors: X
authors: Yang
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China. Electronic address: huangchen_pumc@126.com.
authors: Chen
authors: C
authors: Huang
authors: State Key Laboratory of Cardiovascular Disease, Division of Population Genetics, Fuwai Hospital & National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China. Electronic address: gudongfeng@vip.sina.com.
authors: Dongfeng
authors: D
authors: Gu
mesh_terms: D020413:3' Untranslated Regions; D054058:Acute Coronary Syndrome / Q000097:blood* / Q000473:pathology; D000787:Angina Pectoris / Q000097:blood / Q000473:pathology; D015153:Blotting, Western; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D054357:Chemokine CXCL10 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C111835:CCL2 protein, human; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D016209:Interleukin-8; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
keywords: Acute coronary syndrome; Chemokine; Coactivator-associated arginine methyltransferase 1; miR-15a