Department of Cardiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, , Guangdong, China.
Department of Cardiology, Qingdao Huangdao District People's Hospital, Qingdao, 266400, Shangdong, China.
Eur J Med Res. 2024 Mar 12;29(1):159. doi: 10.1186/s40001-024-01753-3.
Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility.
High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls. A series of bioinformatics tools and databases were used to determine the biological functional classification and pathway enrichment of the circRNAs based on data obtained from sequencing. A hypoxia model was established and used to evaluate the effect of hypoxia on circRNA expression in human cardiomyocytes. A cytoplasmic separation assay and enzyme resistance assay were employed to identify the biological characteristics of circRNA. Polymerase chain reaction validity testing and receiver operating characteristic (ROC) curve analysis were used to evaluate the utility of circRNA assessments in the diagnosis of AMI.
A large number of circRNAs were found to be differentially expressed in the peripheral blood of patients with AMI, and significantly more of these circRNAs were highly expressed than lowly expressed. The genes encoding these circRNAs have a wide range of effects on various functions in the body. A hypoxic environment promoted the upregulation of circRNA expression in human cardiomyocytes, and hsa_circ_0116795 encoded by PPARA was highly expressed in the peripheral blood of the patients with AMI. In terms of biological characteristics, under physiological conditions, hsa_circ_0116795 (circ_PPARA) was mainly located in the cytoplasm of cardiomyocytes and found to be resistant to exonuclease. The ROC curve analysis showed that the expression levels of circ_PPARA in the peripheral blood of patients with AMI were significantly different from those in the peripheral blood of healthy controls.
A large number of abnormally expressed circRNAs are detectable in the peripheral blood of patients with AMI. In particular, circ_PPARA is highly expressed in human myocardial cells under hypoxic conditions, and its biological characteristics indicate that it could be employed as a biomarker for the early diagnosis of AMI.
急性心肌梗死（AMI）是一种严重的心血管疾病，对人类健康造成不良影响。环状 RNA（circRNA）参与 AMI 的病理生理过程，但它们的参与的生物学机制及其临床意义尚不清楚。我们旨在鉴定与 AMI 患者外周血发病率显著相关的 circRNA，并评估其诊断效用。
使用高通量测序筛选 5 例 AMI 患者和 5 例性别和年龄匹配的健康对照者外周血样本中的差异表达 circRNA。使用一系列生物信息学工具和数据库，根据测序数据确定 circRNA 的生物功能分类和途径富集。建立缺氧模型，评估缺氧对人心肌细胞 circRNA 表达的影响。采用细胞质分离和酶抗性试验鉴定 circRNA 的生物学特性。聚合酶链反应有效性检测和受试者工作特征（ROC）曲线分析用于评估 circRNA 评估在 AMI 诊断中的应用价值。
在 AMI 患者外周血中发现大量差异表达的 circRNA，且高表达的 circRNA显著多于低表达的 circRNA。这些 circRNA 编码的基因对机体的各种功能具有广泛的影响。缺氧环境促进人心肌细胞中 circRNA 的表达上调，并且 PPARA 编码的 hsa_circ_0116795 在 AMI 患者外周血中高表达。就生物学特性而言，在生理条件下，hsa_circ_0116795（circ_PPARA）主要位于心肌细胞的细胞质中，且对核酸外切酶具有抗性。ROC 曲线分析显示，AMI 患者外周血中 circ_PPARA 的表达水平与健康对照组外周血中的表达水平有显著差异。
在 AMI 患者外周血中可检测到大量异常表达的 circRNA。特别是，circ_PPARA 在缺氧条件下在人心肌细胞中高表达，其生物学特性表明其可作为 AMI 早期诊断的生物标志物。
