Hypoxia-induced circRNAs encoded by PPARA are highly expressed in human cardiomyocytes and are potential clinical biomarkers of acute myocardial infarction

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.