Circulating microRNA in cardiovascular disease.

Acute myocardial infarction (AMI) and heart failure (HF) are two major causes of cardiovascular mortality and morbidity. Early diagnosis of these conditions is essential to instigate immediate treatment that may result in improved outcomes. Traditional biomarkers of AMI include cardiac troponins and other proteins released from the injured myocardium but there are a number of limitations with these biomarkers especially with regard to specificity. In the past few years circulating nucleic acids, notably microRNA that are small non-coding RNAs that regulate various cellular processes, have been investigated as biomarkers of disease offering improved sensitivity and specificity in the diagnosis and prognostication of various conditions. In this review, the role of microRNAs as biomarkers used in the diagnosis of AMI and HF is discussed, their advantage over traditional biomarkers is outlined and the potential for their implementation in clinical practice is critically assessed.

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 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.

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 <2.0mmol/L) and atherogenic lipoprotein phenotype (ALP; n=10; triglycerides ≥2.0mmol/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.