Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.
Highlights
Cardiovascular diseases (CVD) including Coronary Artery Disease (CAD), stroke and peripheral artery disease are the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems [1,2]
We identified two miRs that significantly correlated with acute non-ST-elevation myocardial infarction (NSTEMI). miR-629-5p was negatively correlated and miR-98-5p was positively correlated (0.21; p = 0.005; false discovery rate (FDR) 0.03) with NSTEMI
Based on vascular tissue samples and comprehensive clinical information from 28 women and 160 men with angiographically confirmed CAD undergoing CABG surgery, we identified 17 novel miRs significantly correlated with cardiovascular risk factors
Summary
Cardiovascular diseases (CVD) including Coronary Artery Disease (CAD), stroke and peripheral artery disease are the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems [1,2]. We recently identified that the MAF bZIP transcription factor F (MAFF) downregulates low-density lipoprotein receptor (LDLR) expression under inflammatory conditions via heterodimerization with BTB domain and CNC homolog 1 (BACH1) and binding at the maf-recognition element in the promoter of LDLR linking two major causes of CAD development–cholesterol metabolism and inflammation [17]. The main challenge is the prioritization of putative functional variants [18,19,20,21,22,23,24,25], as >90% of CAD risk loci are located outside the protein-coding regions [18,19], and seem to affect transcription (promoters, enhancers) and non-coding RNAs, including miRs [26]. Genetic variants can affect the functionality of miRs at all levels, including transcription
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