Institute of Clinical Medicine, University of Oslo (UiO), 0372 Oslo, Norway.
Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.
Int J Mol Sci. 2024 Aug 19;25(16):9014. doi: 10.3390/ijms25169014.
Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab ( = 21) or placebo ( = 19) was collected at admission, 3-7 days, and at 6 months, in addition to samples from healthy controls ( = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3-7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function.
环状 RNA（circRNA）是一类具有重要功能的非编码 RNA，存在于神经系统、心血管系统和癌症中。它们在动脉粥样硬化和心肌梗死（MI）中的作用仍未被充分描述。我们旨在研究动脉粥样硬化形成过程中免疫细胞中的潜在 circRNA，并研究 MI 过程中调节最明显的 circRNA，以及白细胞介素（IL）-6 受体抑制剂托珠单抗的调节作用。野生型（WT）和 小鼠喂食致动脉粥样硬化饮食 10 周，通过 circRNA 微阵列分析 circRNA 谱。收集 ST 段抬高型 MI（STEMI）患者和随机分为托珠单抗（ = 21）或安慰剂（ = 19）组的全血，在入院时、3-7 天和 6 个月时采集，此外还采集了健康对照者的样本（ = 13）。设计了人类 circRNA 的引物，并使用 RT-qPCR 测量 circRNA 水平。通过 RNA 测序研究预测 circRNA 靶标mRNA 的调节。在动脉粥样硬化和 WT 小鼠之间，867 个 circRNA 的表达存在差异。在 STEMI 患者中，circUBAC2 的表达明显低于健康对照组。circANKRD42 和 circUBAC2 的水平与肌钙蛋白 T 呈负相关，而对于 circUBAC2，还与 6 个月时的最终梗死面积呈负相关。研究了 circUBAC2 和 circANKRD42 的预测 mRNA 靶标，并发现了涉及炎症/免疫细胞、细胞凋亡和线粒体功能调节的转录物水平的改变。最后，经皮冠状动脉介入治疗后 3-7 天，托珠单抗诱导 circANKRD42 和 circUBAC2 的上调。STEMI 中 circRNA 水平失调，可能影响免疫系统、细胞凋亡和线粒体功能。
