Taraldsen Maria Dalen, Wiseth Rune, Videm Vibeke, Bye Anja, Madssen Erik
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Cardiology, St. Olavs University Hospital, Trondheim, Norway.
Physiol Genomics. 2022 Apr 1;54(4):129-140. doi: 10.1152/physiolgenomics.00071.2021. Epub 2022 Feb 28.
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. Thirty-one 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 analyzed at baseline and follow-up. Associations between miRs and coronary plaque composition, and the potential effect from exercise, were analyzed using linear regression. 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. 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.
微小RNA（miR）参与动脉粥样硬化发展的不同阶段，并被认为是冠状动脉疾病（CAD）很有前景的生物标志物。我们假设，有氧运动干预前后，循环miR水平与通过射频血管内超声（RF-IVUS）评估的冠状动脉斑块成分相关。研究纳入了31例先前接受过经皮冠状动脉介入治疗（PCI）的CAD患者，这些患者曾参与一项随机试验，该试验将有氧间歇训练（AIT）或中度持续训练（MCT）作为PCI后的干预措施。在基线和随访时，通过灰阶和RF-IVUS分析冠状动脉斑块特征，并分析血浆中预先定义的循环候选miR。使用线性回归分析miR与冠状动脉斑块成分之间的关联以及运动的潜在影响。miR-15a-5p、miR-30e-5p、miR-92a-3p、miR-199a-3p、miR-221-3p和miR-222-3p的循环水平与基线冠状动脉坏死核心体积相关。运动干预后，miR-15a-5p、miR-93-5p和miR-451a水平降低，miR-146a-5p水平升高，与观察到的冠状动脉斑块负荷消退相关。一个mirPath预测工具发现，受miR-15a-5p、miR-199a-3p和miR-30e-5p调控的基因在与脂肪酸生物合成和脂肪酸代谢相关的通路中显著富集。这项探索性研究表明，有六种miR与冠状动脉坏死核心相关，冠状动脉坏死核心是斑块易损性的一个标志物。此外，四种miR的变化与运动干预后冠状动脉斑块负荷的消退相关。这些新发现可能会确定CAD和冠状动脉斑块成分未来潜在的生物标志物。
