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Abstract：
Exosomal microRNAs (miRNAs/miRs) are potential biomarkers for the diagnosis and treatment of cardiovascular disease, and hyperglycemia serves an important role in the development of atherosclerosis. The present study aimed to investigate the expression profile of serum‑derived exosomal miRNAs in coronary heart disease (CHD) with hyperglycemia, and to identify effective biomarkers for predicting coronary artery lesions. Serum samples were collected from eight patients with CHD and hyperglycemia and eight patients with CHD and normoglycemia, exosomes were isolated and differentially expressed miRNAs (DEMIs) were filtered using a human miRNA microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using standard enrichment computational methods for the target genes of DEMIs. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the values of the selected DEMIs in predicting the severity of coronary stenosis. A total of 10 DEMIs, including four upregulated miRNAs (hsa‑let‑7b‑5p, hsa‑miR‑4313, hsa‑miR‑4665‑3p and hsa‑miR‑940) and six downregulated miRNAs (hsa‑miR‑4459, hsa‑miR‑4687‑3p, hsa‑miR‑6087, hsa‑miR‑6089, hsa‑miR‑6740‑5p and hsa‑miR‑6800‑5p), were screened in patients with CHD and hyperglycemia. GO analysis showed that the \'cellular process\', \'single‑organism process\' and \'biological regulation\' were significantly enriched. KEGG pathway analysis revealed that the \'mTOR signaling pathway\', \'FoxO signaling pathway\' and \'neurotrophin signaling pathway\' were significantly enriched. Among these DEMIs, only hsa‑let‑7b‑5p expression was positively correlated with both hemoglobin A1C levels and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. ROC curves showed that hsa‑let‑7b‑5p could serve as an effective biomarker for differentiating the severity of coronary stenosis. In conclusion, the present study demonstrated that serum‑derived exosomal hsa‑let‑7b‑5p is upregulated in patients with CHD and hyperglycemia, and may serve as a noninvasive biomarker for the severity of coronary stenosis.
摘要：
外泌体microRNAs(miRNAs/miRs)是心血管疾病诊断和治疗的潜在生物标志物。高血糖在动脉粥样硬化的发展中起重要作用。本研究旨在探讨血清来源的外泌体miRNAs在冠心病(CHD)伴高血糖的表达谱,并确定预测冠状动脉病变的有效生物标志物。收集8例CHD和高血糖患者和8例CHD和血糖正常患者的血清样本，分离外泌体,并使用人miRNA微阵列过滤差异表达的miRNA(DEMI)。使用标准富集计算方法对DEMI的靶基因进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径分析。应用受试者工作特征（ROC）曲线分析来评估选定的DEMI在预测冠状动脉狭窄严重程度中的价值。共有10个DEMI,包括四个上调的miRNA(hsa‑let‑7b‑5p，hsa‑miR‑4313，hsa‑miR‑4665‑3p和hsa‑miR‑940）和六个下调的miRNA（hsa‑miR‑4459，hsa‑miR‑4687‑3p，hsa‑miR‑6087、hsa‑miR‑6089、hsa‑miR‑6740‑5p和hsa‑miR‑6800‑5p),在冠心病和高血糖患者中进行筛查。GO分析表明，“细胞过程”，“单生物过程”和“生物调节”显著丰富。KEGG通路分析显示，'mTOR信号通路'，“FoxO信号通路”和“神经营养蛋白信号通路”显著富集。在这些DEMI中,只有hsa‑let‑7b‑5p表达与血红蛋白A1C水平呈正相关,并与经皮冠状动脉介入治疗与心脏手术评分之间的协同作用呈正相关.ROC曲线显示，hsa‑let‑7b‑5p可以作为区分冠状动脉狭窄严重程度的有效生物标志物。总之,本研究表明，血清来源的外泌体hsa-let-7b-5p在CHD和高血糖患者中上调，并且可以作为冠状动脉狭窄严重程度的非侵入性生物标志物。
