title: Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells.
abstract: BACKGROUND
  Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in atherosclerotic coronary heart disease. Therefore, exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.
  
  
  METHODS
  The myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The influence of lovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours. Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were analyzed with immunoblotting.
  
  
  RESULTS
  Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%± 34.32% of control levels (P = 0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure up-regulated PPP1R3A to 143.85%± 21.89% of control levels in cardiomyocytes (P = 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P = 0.0077), this effect was significantly (P = 0.018) blunted when miR-21 was functionally inhibited.
  
  
  CONCLUSIONS
  miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of lovastatin.
authors.affiliation: Department of Clinical Pharmacology, Aerospace Central Hospital, Beijing 100049, China. Email: gwz501@hotmail.com.
authors.forename: Weizao
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Clinical Pharmacology, Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Huichen
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Fuwai Heart Hospital & Cardiovascular Institute, Chinese Medical Academy, Beijing 100037, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, Aerospace Central Hospital, Beijing 100049, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Du
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D008148:Lovastatin; C114205:PPP1R3A protein, human; D010749:Phosphoprotein Phosphatases