Fan James, Gemel Joanna, Beyer Eric C, Lapping-Carr Gabrielle
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Int J Mol Sci. 2025 Apr 18;26(8):3831. doi: 10.3390/ijms26083831.
Acute chest syndrome (ACS) is among the most serious complications of sickle cell disease (SCD). While the pathogenesis of ACS is incompletely understood, endothelial damage and microvascular occlusion are critical components. Our previous studies have implicated small extracellular vesicles in the plasma of subjects with SCD in causing endothelial dysfunction. This suggested that microRNAs within these small EVs might be responsible for endothelial damage. The sequencing of microRNAs in small EVs from the plasma of subjects with SCD revealed that several miRNAs were differentially expressed between subjects with and without ACS history, including let-7c-5p. In a replication cohort, plasma let-7c-5p levels were quantified via RT-qPCR. The baseline plasma let-7c-5p level was twofold higher in patients without previous ACS. Furthermore, we observed a positive correlation between let-7c-5p levels and time to subsequent ACS events. These findings suggest a role for let-7c-5p in endothelial disruption underlying ACS pathogenesis. It may also serve as a novel biomarker for ACS detection and the prediction of disease progression.
急性胸综合征（ACS）是镰状细胞病（SCD）最严重的并发症之一。虽然ACS的发病机制尚未完全明确，但内皮损伤和微血管闭塞是关键因素。我们之前的研究表明，SCD患者血浆中的小细胞外囊泡会导致内皮功能障碍。这表明这些小细胞外囊泡中的微小RNA（miRNA）可能是内皮损伤的原因。对SCD患者血浆中小细胞外囊泡的miRNA进行测序发现，有ACS病史和无ACS病史的患者之间有几种miRNA表达存在差异，包括let-7c-5p。在一个重复队列中，通过逆转录定量聚合酶链反应（RT-qPCR）对血浆中let-7c-5p的水平进行了定量。既往无ACS的患者血浆中let-7c-5p的基线水平高出两倍。此外，我们观察到let-7c-5p水平与后续ACS事件发生时间之间存在正相关。这些发现表明let-7c-5p在ACS发病机制中内皮破坏方面发挥作用。它也可能作为ACS检测和疾病进展预测的一种新型生物标志物。
