The Lydia and Carol Kittner, Lea and Benjamin Davidai Division of Cardiovascular Medicine and Surgery and Research Institute, Tzafon Medical Center, Affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Tiberias 1528001, Israel.
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Int J Mol Sci. 2023 May 10;24(10):8551. doi: 10.3390/ijms24108551.
Coronary artery disease (CAD) is the leading cause of mortality worldwide. In chronic and myocardial infarction (MI) states, aberrant levels of circulating microRNAs compromise gene expression and pathophysiology. We aimed to compare microRNA expression in chronic-CAD and acute-MI male patients in peripheral blood vasculature versus coronary arteries proximal to a culprit area. Blood from chronic-CAD, acute-MI with/out ST segment elevation (STEMI/NSTEMI, respectively), and control patients lacking previous CAD or having patent coronary arteries was collected during coronary catheterization from peripheral arteries and from proximal culprit coronary arteries aimed for the interventions. Random coronary arterial blood was collected from controls; RNA extraction, miRNA library preparation and Next Generation Sequencing followed. High concentrations of microRNA-483-5p (miR-483-5p) were noted as 'coronary arterial gradient' in culprit acute-MI versus chronic-CAD ( = 0.035) which were similar to controls versus chronic-CAD ( < 0.001). Meanwhile, peripheral miR-483-5p was downregulated in acute-MI and chronic-CAD, compared with controls (1.1 ± 2.2 vs. 2.6 ± 3.3, respectively, < 0.005). A receiver operating characteristic curve analysis for miR483-5p association with chronic CAD demonstrated an area under the curve of 0.722 ( < 0.001) with 79% sensitivity and 70% specificity. Using in silico gene analysis, we detected miR-483-5p cardiac gene targets, responsible for inflammation (), oxidative stress (, ), apoptosis (), fibrosis (, , ), angiogenesis (, ) and wound healing (). High miR-483-5p 'coronary arterial gradient' in acute-MI, unnoticed in chronic-CAD, suggests important local mechanisms for miR483-5p in CAD in response to local myocardial ischemia. MiR-483-5p may have an important role as a gene modulator for pathologic and tissue repair states, is a suggestive biomarker, and is a potential therapeutic target for acute and chronic cardiovascular disease.
冠心病（CAD）是全球死亡的主要原因。在慢性和心肌梗死（MI）状态下，循环 microRNA 的异常水平会影响基因表达和病理生理学。我们旨在比较慢性 CAD 和急性 MI 男性患者外周血管和靠近罪犯区域的冠状动脉中 microRNA 的表达。在冠状动脉造影期间，从外周动脉和旨在进行干预的近端罪犯冠状动脉采集患有慢性 CAD、无 ST 段抬高的急性 MI（分别为 STEMI/NSTEMI）和缺乏先前 CAD 或具有通畅冠状动脉的对照患者的血液。从对照者中随机采集冠状动脉血液；提取 RNA，制备 microRNA 文库，进行下一代测序。在罪犯性急性 MI 与慢性 CAD 相比，miR-483-5p（miR-483-5p）的高浓度表现为“冠状动脉梯度”（ = 0.035），与对照者与慢性 CAD 相比相似（ < 0.001）。同时，与对照者相比，急性 MI 和慢性 CAD 中外周 miR-483-5p 下调（分别为 1.1 ± 2.2 与 2.6 ± 3.3， < 0.005）。miR483-5p 与慢性 CAD 相关性的受试者工作特征曲线分析显示曲线下面积为 0.722（ < 0.001），灵敏度为 79%，特异性为 70%。使用计算机基因分析，我们检测到 miR-483-5p 心脏基因靶标，负责炎症（）、氧化应激（、）、细胞凋亡（）、纤维化（、、）、血管生成（、）和伤口愈合（）。急性 MI 中 miR-483-5p 的高“冠状动脉梯度”在慢性 CAD 中未被发现，这表明 miR483-5p 在局部心肌缺血时在 CAD 中具有重要的局部机制。miR-483-5p 可能作为一种基因调节剂在病理和组织修复状态中发挥重要作用，是一种有提示意义的生物标志物，也是急性和慢性心血管疾病的潜在治疗靶点。
