title: Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins.
abstract: BACKGROUND
  Small non-coding microRNAs (miR) have important regulatory roles and are used as biomarkers of disease. We investigated the relationship between lipoproteins and circulating miR-30c, evaluated how they are transported in circulation and determined whether statins altered the circulating concentration of miR-30c.
  
  
  METHODS
  To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated. Ultracentrifugation and nanoparticle tracking analysis was used to evaluate the transportation of miR-30c in the circulation by lipoproteins and extracellular vesicles in three healthy volunteers. Using archived samples from previous studies, the effects of 40mg rosuvastatin (n=22) and 40mg pravastatin (n=24) on miR-30c expression was also examined. RNA extraction, reverse transcription-quantitative real-time polymerase chain reaction was carried out using standard procedures.
  
  
  RESULTS
  When stratified according to total cholesterol concentration, there was increased miR-30c expression in the highest compared to the lowest tertile (p=0.035). There was significant positive correlation between miR-30c and total- (r=0.367; p=0.002) and LDL-cholesterol (r=0.391; p=0.001). We found that miR-30c was transported in both exosomes and on HDL3. There was a 3.8-fold increased expression of circulating miR-30c after pravastatin treatment for 1year (p=0.005) but no significant change with atorvastatin after 8weeks (p=0.145).
  
  
  CONCLUSIONS
  This study shows for the first-time in humans that circulating miR-30c is significantly, positively correlated with total- and LDL-cholesterol implicating regulatory functions in lipid homeostasis. We show miR-30c is transported in both exosomes and on HDL3 and pravastatin therapy significantly increased circulating miR-30c expression adding to the pleiotropic dimensions of statins.
authors.affiliation: Department of Biochemistry, Royal Lancaster Infirmary & Furness General Hospital, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, United Kingdom; Lancaster Medical School, University of Lancaster, Lancaster, United Kingdom. Electronic address: Ravinder.Sodi@mbht.nhs.uk.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Sodi
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom.
authors.forename: Jarlath
authors.initials: J
authors.lastname: Eastwood
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom.
authors.forename: Muriel
authors.initials: M
authors.lastname: Caslake
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Packard
authors.affiliation: British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Denby
mesh_terms: D000328:Adult; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008055:Lipids / Q000502:physiology; D053440:Lipoproteins, HDL3 / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology; D000068718:Rosuvastatin Calcium / Q000494:pharmacology
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D053440:Lipoproteins, HDL3; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D017035:Pravastatin
keywords: Cholesterol; Circulating microRNA; Lipoproteins; Statins; miR-30c