Associations between circulating microRNAs and coronary plaque characteristics: potential impact from physical exercise

Abstract

Background and aims MicroRNAs (miRs) are involved in different steps in the development of atherosclerosis and are proposed as promising biomarkers of coronary artery disease (CAD). We hypothesized that circulating levels of miRs were associated with coronary plaque components assessed by radiofrequency intravascular ultrasound (RF-IVUS) before and after aerobic exercise intervention. Methods 31 patients with CAD treated with percutaneous coronary intervention (PCI) previously included in a randomized trial with aerobic interval training (AIT) or moderate continuous training (MCT) as post-PCI intervention were included. Coronary plaque characteristics by grayscale and RF-IVUS and predefined circulating candidate miRs in plasma were analysed at baseline and follow-up. Associations between miRs and coronary plaque composition, and the potential effect from exercise, were analysed using linear regression. Results Circulating levels of miR-15a-5p, miR-30e-5p, miR-92a-3p, miR-199a-3p, miR-221-3p, and miR-222-3p were associated with baseline coronary necrotic core volume. Following exercise intervention, decreased levels of miR-15a-5p, miR-93-5p, and miR-451a, and increased levels of miR-146a-5p were associated with an observed regression of coronary plaque burden. A mirPath prediction tool identified that genes regulated by miR-15a-5p, miR-199a-3p, and miR-30e-5p were significantly overrepresented in pathways related to fatty acid biosynthesis and fatty acid metabolism. Conclusion This exploratory study demonstrated six miRs associated with coronary necrotic core, a marker of plaque vulnerability. In addition, changes in four miRs were associated with a regression of coronary plaque burden following exercise intervention. These novel findings may identify potential future biomarkers of CAD and coronary plaque composition.

Associations between circulating microRNAs and lipid-rich coronary plaques measured with near-infrared spectroscopy

“…These studies were limited by the inclusion of few predefined candidate miRs with 21 analyzed miRs in total, and miR-133b was not among the analyzed miRs. One recent IVUS study found six circulating plasma miRs (miR-15a-5p, miR-30e-5p, miR-92a-3p, miR-199a-3p, miR-221-3p, and miR-222-3p) to be associated with coronary plaque necrotic core volume, and three miRs (miR-15a-5p, miR-93-5p, and miR-451a) to be associated with observed regression of plaque burden after 12 weeks of aerobic exercise 17 . Interestingly, miR-15a-5p, miR-30e-5p, and miR-199a-3p were found be involved in regulation of atherosclerosis-related pathways, including fatty acid biosynthesis and metabolism.…”

Non-Invasive Modalities in the Assessment of Vulnerable Coronary Atherosclerotic Plaques

“…Adequately sized clinical trials should be designed to assess the importance of combining circulating biomarkers with imaging features for the detection of VCAPs. Moreover, microRNAs are being investigated in the management of atherosclerotic diseases [ 37 , 38 ], and preliminary results have associated their levels with vulnerable plaque characteristics [ 39 ].…”

miRNA in Ischemic Heart Disease and Its Potential as Biomarkers: A Comprehensive Review

“…Targeting miRNAs with anti-miRNAs, which are modified antisense oligonucleotides carrying the complementary reverse sequence of a mature miRNA, can neutralise the function of aberrantly expressed miRNAs and promote desired gene expression, whereas the use of miRNA mimics can stimulate the natural role of miRNAs to suppress gene expression and bring beneficial effects. Combination therapy of miRNAs with physical exercise has shown promising results in regression of coronary plaque burden [ 52 ]. However, the delivery of an appropriate therapeutic range of miRNAs to arteries is tricky considering the low effectiveness of direct injection [ 53 ].…”