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

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

The association of circulating microRNA-30c with atherogenic lipoprotein subfractions and composition

Circulating miR-30c has been linked to various aspects of cholesterol homeostasis. The aim of this study was to determine the association of circulating miR-30c with the atherogenic lipoprotein subfractions. Samples from subjects who were given placebo (n = 22) in a randomised, double-blind crossover study were used. Subjects were divided into non-atherogenic lipoprotein phenotype (Non-ALP; n = 12; triglycerides < 2.0 mmol/L) and atherogenic lipoprotein phenotype (ALP; n = 10; triglycerides ≥ 2.0 mmol/L) groups. All lipid and lipoprotein measurements, RNA extraction and reverse transcription-quantitative real-time polymerase chain reaction were undertaken using standard procedures. Subjects with ALP weighed significantly more than their non-ALP counterparts (p = 0.023). In the non-ALP group there was significant correlation between miR-30c and components within VLDL1, namely triglyceride which showed a negative association (p = 0.035) whereas phospholipids and cholesterol-ester were both positively correlated (p = 0.025 and 0.014, respectively). In contrast, in the ALP group there was a significant correlation between the expression of miR-30c and components within VLDL2, namely triglyceride, which was positively associated (p = 0.013). This study reveals specificity with regards to the effect of miR-30c on VLDL subfractions based on the individual's lipoprotein phenotype and implicates roles for microsomal-triglyceride transfer-protein and cholesteryl-ester-transfer-protein in LDL and VLDL metabolism, respectively