Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis
Abstract Background Fulminant myocarditis (FM), a critical cardiac disease, is characterised by atypical initial symptoms and rapid progression and tends to lead to cardiomyocyte degeneration or necrosis. Reliable biological markers for FM screening remain lacking. Circular RNAs (circRNAs) are highl...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-025-02333-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825197366106390528 |
|---|---|
| author | Shasha Huang Shumin He Fei Xiao Yang Zhou Su Lyu |
| author_facet | Shasha Huang Shumin He Fei Xiao Yang Zhou Su Lyu |
| author_sort | Shasha Huang |
| collection | DOAJ |
| description | Abstract Background Fulminant myocarditis (FM), a critical cardiac disease, is characterised by atypical initial symptoms and rapid progression and tends to lead to cardiomyocyte degeneration or necrosis. Reliable biological markers for FM screening remain lacking. Circular RNAs (circRNAs) are highly stable in peripheral blood due to their special closed-loop structure, and reports have described their involvement in regulating inflammatory responses and cell injury in cardiomyocytes. This study attempted to identify the abnormal expression of circRNAs in the peripheral blood of patients with FM and to evaluate the potential diagnostic value. Methods Peripheral blood was collected from 5 children with FM and 5 sex- and age-matched healthy controls; total RNA was extracted from each sample, and the extracted RNA from each group was pooled. After RNase R treatment, high-throughput sequencing was performed to screen for differentially expressed circRNAs in the peripheral blood of patients. Biological function classification and enrichment analysis were used to explore the main action pathways involving differentially expressed circRNAs. A lipopolysaccharide (LPS)-induced cardiomyocyte inflammation model was used to explore the effect of inflammation on the expression of these dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the potential clinical value of FM-related circRNAs as biomarkers in a large sample of patients. Results CircRNA expression profiling of peripheral blood samples from patients revealed 6,435 and 3,678 circRNAs with upregulated and downregulated expression, respectively, compared with healthy controls. The expression of 1,749 circRNAs did not significantly differ between the groups. GO and KEGG analysis revealed that the genes encoding the dysregulated circRNAs were associated with various biological functions related to the risk of FM development, including infectious diseases, the immune system, and signal transduction. The high expression of hsa_circ_0064338 (circ_PPARG) was confirmed in both the myocardial cell inflammation model and peripheral blood from a large sample of FM patients. ROC curve analysis showed that the level of circ_PPARG in peripheral blood had a good ability to distinguish patients with FM from healthy controls. Conclusions Large numbers of abnormally regulated circRNAs were identified in peripheral blood from patients with FM; among these, the highly expressed circ_PPARG could distinguish patients from healthy controls to a certain extent. It is expected to become a potential clinical biomarker of FM in the future. |
| format | Article |
| id | doaj-art-9026d80dac5c46b9a02c9a217b83c1f5 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-9026d80dac5c46b9a02c9a217b83c1f52025-02-09T12:26:38ZengBMCEuropean Journal of Medical Research2047-783X2025-02-0130111210.1186/s40001-025-02333-9Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditisShasha Huang0Shumin He1Fei Xiao2Yang Zhou3Su Lyu4Department of Cardiology, Shenzhen People’s Hospital The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and TechnologyDepartment of Infectious Diseases, Zibo Ninth People’s HospitalDepartment of Cardiology, Zibo Central HospitalDepartment of Pain Management, Zhongshan City People’s HospitalDepartment of Critical Medicine, The Friendship Hospital of Ily Kazak Autonomous PrefectureAbstract Background Fulminant myocarditis (FM), a critical cardiac disease, is characterised by atypical initial symptoms and rapid progression and tends to lead to cardiomyocyte degeneration or necrosis. Reliable biological markers for FM screening remain lacking. Circular RNAs (circRNAs) are highly stable in peripheral blood due to their special closed-loop structure, and reports have described their involvement in regulating inflammatory responses and cell injury in cardiomyocytes. This study attempted to identify the abnormal expression of circRNAs in the peripheral blood of patients with FM and to evaluate the potential diagnostic value. Methods Peripheral blood was collected from 5 children with FM and 5 sex- and age-matched healthy controls; total RNA was extracted from each sample, and the extracted RNA from each group was pooled. After RNase R treatment, high-throughput sequencing was performed to screen for differentially expressed circRNAs in the peripheral blood of patients. Biological function classification and enrichment analysis were used to explore the main action pathways involving differentially expressed circRNAs. A lipopolysaccharide (LPS)-induced cardiomyocyte inflammation model was used to explore the effect of inflammation on the expression of these dysregulated circRNAs. Receiver operating characteristic (ROC) curves were used to evaluate the potential clinical value of FM-related circRNAs as biomarkers in a large sample of patients. Results CircRNA expression profiling of peripheral blood samples from patients revealed 6,435 and 3,678 circRNAs with upregulated and downregulated expression, respectively, compared with healthy controls. The expression of 1,749 circRNAs did not significantly differ between the groups. GO and KEGG analysis revealed that the genes encoding the dysregulated circRNAs were associated with various biological functions related to the risk of FM development, including infectious diseases, the immune system, and signal transduction. The high expression of hsa_circ_0064338 (circ_PPARG) was confirmed in both the myocardial cell inflammation model and peripheral blood from a large sample of FM patients. ROC curve analysis showed that the level of circ_PPARG in peripheral blood had a good ability to distinguish patients with FM from healthy controls. Conclusions Large numbers of abnormally regulated circRNAs were identified in peripheral blood from patients with FM; among these, the highly expressed circ_PPARG could distinguish patients from healthy controls to a certain extent. It is expected to become a potential clinical biomarker of FM in the future.https://doi.org/10.1186/s40001-025-02333-9Fulminant myocarditisPPARGCircRNAsROC curveBiomarker |
| spellingShingle | Shasha Huang Shumin He Fei Xiao Yang Zhou Su Lyu Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis European Journal of Medical Research Fulminant myocarditis PPARG CircRNAs ROC curve Biomarker |
| title | Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| title_full | Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| title_fullStr | Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| title_full_unstemmed | Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| title_short | Circular RNA encoded by PPARG in the peripheral blood and a lipopolysaccharide-induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| title_sort | circular rna encoded by pparg in the peripheral blood and a lipopolysaccharide induced cardiomyocyte inflammation model is identified as a marker of fulminant myocarditis |
| topic | Fulminant myocarditis PPARG CircRNAs ROC curve Biomarker |
| url | https://doi.org/10.1186/s40001-025-02333-9 |
| work_keys_str_mv | AT shashahuang circularrnaencodedbyppargintheperipheralbloodandalipopolysaccharideinducedcardiomyocyteinflammationmodelisidentifiedasamarkeroffulminantmyocarditis AT shuminhe circularrnaencodedbyppargintheperipheralbloodandalipopolysaccharideinducedcardiomyocyteinflammationmodelisidentifiedasamarkeroffulminantmyocarditis AT feixiao circularrnaencodedbyppargintheperipheralbloodandalipopolysaccharideinducedcardiomyocyteinflammationmodelisidentifiedasamarkeroffulminantmyocarditis AT yangzhou circularrnaencodedbyppargintheperipheralbloodandalipopolysaccharideinducedcardiomyocyteinflammationmodelisidentifiedasamarkeroffulminantmyocarditis AT sulyu circularrnaencodedbyppargintheperipheralbloodandalipopolysaccharideinducedcardiomyocyteinflammationmodelisidentifiedasamarkeroffulminantmyocarditis |