title: Deregulated hepatic microRNAs underlie the association between non-alcoholic fatty liver disease and coronary artery disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) appears to be a new risk factor for the development of coronary artery disease (CAD). Members of a class of non-coding RNAs, termed microRNAs (miRNAs), have been identified as post-transcriptional regulators of cholesterol homoeostasis and can contribute to the development of NAFLD. The aims of this study were to (i) to assess the relationship between NAFLD and sudden cardiac death (SCD) from severe CAD in forensic autopsies and (ii) to quantify several hepatic miRNAs previously associated with lipid metabolism and NAFLD to correlate their expression with the presence of NAFLD, CAD, obesity parameters and postmortem lipid profile.
  
  
  
  A total of 133 cases of autopsies with SCD and established CAD (patient group, CAD-SCD) and 106 cases of non-CAD sudden death (control group, non-CAD-SD) were included. miRNAs were quantified in frozen liver tissues.
  
  
  
  Males predominated in both groups. Patients more frequently exhibited NAFLD and necroinflammatory steatohepatitis (NASH) than controls (62% vs 26%, P = 0.001 and 42% vs 26%, P = 0.001 respectively). In both groups, the presence of NAFLD correlated with body mass index and abdominal circumference (P < 0.05). An increase in miR-34a-5p and a decrease in miR-122-5p and -29c-3p in patients with NASH vs controls without NAFLD were observed (P < 0.05). Finally, significant correlations between miR-122-5p and unfavourable lipid profile and also hs-CRP and miR-34a-5p were noted.
  
  
  
  CAD is associated with NAFLD and NASH. The hepatic miRNAs studied appear to be associated with NAFLD severity and may promote CAD through lipid metabolism alteration and/or promotion of the systemic inflammation.
authors.affiliation: Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Aitana
authors.initials: A
authors.lastname: Braza-Boïls
authors.affiliation: Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Marí-Alexandre
authors.affiliation: Servicio de Patología, Instituto de Medicina Legal, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Molina
authors.affiliation: Servcicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Arnau
authors.affiliation: Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Moisés
authors.initials: M
authors.lastname: Barceló-Molina
authors.affiliation: Servcicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Domingo
authors.affiliation: Servicio de Análisis Clínicos, Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Girbes
authors.affiliation: Servicio de Patología, Instituto de Medicina Legal, Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Giner
authors.affiliation: Servcicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.affiliation: Servcicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Zorio
mesh_terms: D000328:Adult; D001344:Autopsy; D003324:Coronary Artery Disease / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D013030:Spain
chemical_list: D035683:MicroRNAs
keywords: ischaemic heart disease; microRNAs; steatohepatitis; sudden cardiac death