Peña-Peña Mario, Zepeda-García Óscar, Posadas-Sánchez Rosalinda, Sánchez-Muñoz Fausto, Domínguez-Pérez Mayra, Martínez-Greene Juan Alfonso, López-Bautista Fabiola, Hernández-Díazcouder Adrián, Jiménez-Ortega Rogelio F, Valencia-Cruz Alejandra Idan, Nuñez-Salgado Adrián, Mani-Arellano Isaac Emanuel, Martínez-Flores Karina, Villarreal-Molina Teresa, Martínez-Martínez Eduardo, Jacobo-Albavera Leonor
Sección de Estudios de Posgrado, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.
Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Int J Mol Sci. 2025 Sep 7;26(17):8727. doi: 10.3390/ijms26178727.
Subclinical coronary atherosclerosis (SCA) is an early stage of coronary artery disease (CAD) that often goes unrecognized until clinical events occur. Identifying circulating molecular biomarkers could improve early diagnosis and risk assessment in asymptomatic individuals. This study employed a two-phase approach to identify plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) associated with SCA. In the discovery phase, plasma samples from male participants were analyzed using Affymetrix GeneChip miRNA 4.0 microarrays. Differentially expressed miRNAs were refined through bioinformatic analysis, cross-species comparison with murine data, and target gene prediction. In the validation phase, six candidate miRNAs were quantified by RT-qPCR in an independent cohort. Six miRNAs were differentially expressed between individuals with SCA and controls. Among these, the combination of miR-146b-5p, miR-4701-3p, and miR-1180-3p demonstrated a high discriminative capacity for SCA (AUC = 0.8281; sensitivity = 93.75%; specificity = 93.75%). Functional enrichment analysis revealed that predicted target genes are involved in key atherosclerosis-related pathways, including inflammation, lipid metabolism, and vascular remodeling. EV-derived miRNAs may serve as non-invasive biomarkers for the early detection of coronary atherosclerosis. These findings provide insight into the molecular processes underlying subclinical vascular disease and support the integration of EV-associated miRNAs into preventive cardiology strategies.
亚临床冠状动脉粥样硬化（SCA）是冠状动脉疾病（CAD）的早期阶段，通常在临床事件发生之前未被识别。识别循环分子生物标志物可以改善无症状个体的早期诊断和风险评估。本研究采用两阶段方法来识别与SCA相关的血浆细胞外囊泡（EV）衍生的微小RNA（miRNA）。在发现阶段，使用Affymetrix GeneChip miRNA 4.0微阵列分析男性参与者的血浆样本。通过生物信息学分析、与小鼠数据的跨物种比较和靶基因预测来优化差异表达的miRNA。在验证阶段，在一个独立队列中通过RT-qPCR对六个候选miRNA进行定量。SCA患者和对照组之间有六个miRNA差异表达。其中，miR-146b-5p、miR-4701-3p和miR-1180-3p的组合对SCA具有高鉴别能力（AUC = 0.8281；敏感性 = 93.75%；特异性 = 93.75%）。功能富集分析表明，预测的靶基因参与关键的动脉粥样硬化相关途径，包括炎症、脂质代谢和血管重塑。EV衍生的miRNA可作为冠状动脉粥样硬化早期检测的非侵入性生物标志物。这些发现为亚临床血管疾病的分子过程提供了见解，并支持将EV相关的miRNA纳入预防性心脏病学策略。
