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

Sodi, Ravinder, Eastwood, Jarlath, Caslake, Muriel, Packard, Chris J. ORCID: https://orcid.org/0000-0002-2386-9927 and Denby, Laura(2017) Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins.Clinica Chimica Acta, 466, pp. 13-19. (doi: 10.1016/j.cca.2016.12.031) (PMID:28062296)

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 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 1 year (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 miR-30c expression adding to the pleiotropic dimensions of statins.

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