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
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