Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Abstract

Despite the promising value of miRnAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profile and affect their results. This study determines if the blood starting material is a source of variance in miRNA profile by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a significant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, different patterns of miRNA expression between serum and plasma. Although NSTEMI modified the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p < 0.01). For miR-133a and miR-26a, differences were only detected in serum (p = 0.0240), and conversely, miR-499a showed differences only in plasma of NSTEMI (p = 0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2 −ΔΔct : 5.7, p = 0.0221) and decreased in plasma (2 −ΔΔct : 0.5, p = 0.0107). Plasma and serum exhibit different patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with different starting material could not be comparable. MicroRNAs (miRNA) are highly conserved small noncoding RNAs that regulate post-transcriptional gene expression 1. Through this mechanism, miRNAs regulate silencing of gene expression and can modify cell and tissue phenotype. Even though the existence of miRNAs and their mechanisms of action are not recent discoveries, the clinical implications of these micro molecules are relatively new and still a focus of debate. miRNAs can act intracellularly 1 or be actively secreted by cells and contribute to intercellular or cell-tissue communication 1. miR-NAs are remarkably stable in human biofluids 2 , including plasma and serum, due to their packaging into membranous vesicles including exosomes, microvesicles, and apoptotic bodies, and to the association to RNA-binding proteins, such as the Argonaute family of lipoprotein complexes like high-density lipoprotein 3. As a result, circulating miRNAs have emerged as powerful diagnostic or prognostic biomarkers in different pathophysiological conditions, including cardiovascular disease (CVD) 4. A large number of independent clinical studies and basic science in animal models have described distinct patterns of miRNA expression in CVD and associated risk factors, reinforcing the potential use of miRNA as

An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics

“…A literature review pointed out miR-16, miR-93, miR-106-5p and miR-484 as putative normalizers in plasma samples [ 24 , 25 , 26 , 27 ]. These four normalizers were tested in all samples of the present study, and the best panel was determined using geNorm algorithm [ 28 ].…”

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction—Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage

“…The 90% of the human genome is transcribed in non-coding RNAs, which are classified according to their length in microRNAs (miRNA) and long non-coding RNAs (lncRNA) [ 32 ]. Both of them have recently been identified as contributors to HF development [ 32 , 33 , 34 ].…”

“…Nowadays, it is widely accepted that circulating miRNA expression profiles can provide new insights in predicting HF among asymptomatic patients. MiRNAs are short, single-stranded, non-coding RNA molecules, packaged into membranous vesicles such as exosomes, microvesicles, and apoptotic bodies, playing a major role in negative post-transcriptional regulation of gene expression [ 33 , 34 ]. Given their presence and high stability in human fluids such as plasma and serum, they are attractive candidates for disease identification and monitoring [ 33 , 35 ].…”

miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

“…Inconsistencies and variations in results between studies can mostly be attributed to pre-analytical variation arising from different protocols as well as different normalization strategies. The use of plasma or serum, the purification technique, batch effects, the anticoagulant used, leukocyte and platelet contamination, hemolysis, sample storage time, quantification technique are important factors that influence miRNA plasma level variability observed between studies [117][118][119][120] . In addition, in order to obtain enough statistical power, cohorts have to be well calculated to obtain consistent and reproducible results.…”