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Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins

Research output: Contribution to journalArticle

  • Ravinder Sodi
  • Jarlath Eastwood
  • Muriel Caslake
  • Chris J Packard
  • Laura Denby

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    Rights statement: This is the authors accepted manuscript as accepted by Clin Chim Acta on the 30/12/16

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Original languageEnglish
Pages (from-to)13-19
JournalClinica chimica acta; international journal of clinical chemistry
Volume466
Early online date3 Jan 2017
DOIs
Publication statusPublished - Mar 2017

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 40 mg rosuvastatin (n = 22) and 40 mg pravastatin (n = 24) on miR-30c expression was also examined. RNA extraction, reverse transcriptionquantitative 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 1-y (p=0.005) but no significant change with atorvastatin after 8-weeks (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 4 miR-30c expression adding to the pleiotropic dimensions of statins.

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