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Expression of microRNA-514a-5p and its biological function in experimental pulmonary thromboembolism

机译:microRNA-514a-5p在实验性肺血栓栓塞中的表达及其生物学功能

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摘要

It is difficult to diagnose pulmonary thromboembolism (PTE) in clinical practice. While microRNAs (miRNAs) have been widely investigated as biomarkers for various diseases, their value as biomarkers for PTE remains largely unknown. In the present study, 83 miRNAs showed altered expression in an intermediate-risk PTE group when compared with their expression in a low-risk PTE group as detected by miRNA microarray analysis. After reviewing those data, hsa-miR-514a-5p was selected as a potential biomarker for PTE progression. Disordered myocardial fibroblast arrangements, broadened intercellular spaces, diapedesis of erythrocytes, and lower numbers of nuclei in the right ventricular wall were observed in rats in a PTE model group when compared to rats in a normal saline (NS) group. Furthermore, hyperexpression of miR-514a-5p exacerbated the morphological characteristics of lung and right ventricular tissues, and caused increased RVHI and lung index values, as well as increased BNP and NT-pro-BNP levels in the PTE model rats, possibly by downregulating Chordin-like 1 (CHRDL1) expression. These results suggest that MiR-514a-5p helps to exasperate PTE development by promoting several aspects of PTE pathology, including inflammation, lung injury, and right ventricular hypertrophy by targeting CHRDL1.
机译:在临床实践中很难诊断出肺血栓栓塞症(PTE)。尽管microRNA(miRNA)作为各种疾病的生物标记物已被广泛研究,但它们作为PTE生物标记物的价值仍然未知。在本研究中,与miRNA微阵列分析检测到的低风险PTE组中的表达相比,中等风险PTE组中的83个miRNA表达有所改变。审查这些数据后,选择hsa-miR-514a-5p作为PTE进展的潜在生物标志物。与正常生理盐水(NS)组的大鼠相比,在PTE模型组的大鼠中观察到了紊乱的心肌成纤维细胞排列,扩大的细胞间间隙,红细胞的渗血和右心室壁核数减少。此外,miR-514a-5p的过表达加剧了肺和右心室组织的形态学特征,并可能通过下调PTE模型大鼠的RVHI和肺指数值,以及增加BNP和NT-pro-BNP水平Chordin-like 1(CHRDL1)表达。这些结果表明,MiR-514a-5p通过靶向CHRDL1促进PTE病理学的多个方面(包括炎症,肺损伤和右心室肥大),有助于激怒PTE的发展。

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