CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 98 AFRICA CircRNA-mediated pathology: a new preliminary insight into the mechanism of type II cardio-renal syndrome Huan Wang, Yuanhui Hu, Jingjing Shi, Huaqin Wu, Zhiling Qiu, Yanting Geng Abstract Aim: The aim of this research was to investigate the expression of peripheral blood circular RNA (circRNA) in patients with type II cardio-renal syndrome, uncover the potential function and possible mechanisms mediated by circRNAs, and ultimately provide gene target support for the treatment of type II cardio-renal syndrome. Methods: CircRNAs in the peripheral blood from five healthy individuals and 20 type II cardio-renal syndrome patients were collected for micro-array analysis. Another cohort study consisting of 12 normal cases and 15 type II cardiorenal syndrome patients was conducted to verify the chosen circRNA by quantitative real-time polymerase chain reaction. Results: A total of 2 884 circRNAs were found to be differentially expressed in the group of patients with type II cardio-renal syndrome. Of these, 1 989 were upregulated and 895 were downregulated. One circRNA was then selected as a candidate biomarker and further validated in the second cohort. Conclusion: Differentially expressed mRNAs between patients with type II cardio-renal syndrome and healthy controls were enriched in two pathways, including haematopoietic cell lineage and cell adhesion molecules. CircRNA-mediated pathology is indispensable and plays an important role in the progress of type II cardio-renal syndrome. More importantly, hsa_cir_0001763 may be an important character in circRNAmediated pathology. Keywords: circular RNA, micro-array, quantitative real-time polymerase chain reaction, type II cardio-renal syndrome Submitted 31/3/21, accepted 14/6/22 Published online 10/3/23 Cardiovasc J Afr 2023; 34: 98–103 www.cvja.co.za DOI: 10.5830/CVJA-2022-033 Heart failure is the terminal stage in the development of heart disease. An epidemiological survey of chronic heart failure carried out by the European Society of Cardiology found that the incidence of chronic heart failure symptoms in Europe was 0.4 to 2%.1 The prevalence of chronic heart failure in the USA is approximately 1.5 to 2.0% and among them, patients over 65 years can reach six to 10%.2 The prevalence of heart failure in the northern part of China is about three times that of the south.3 Heart failure has become an important public health problem for human health. Proteinuria and declining glomerular filtration rate (GFR) are independent risk factors for the progression of cardiovascular diseases.4 Type II cardio-renal syndrome refers to chronic abnormalities in cardiac functioning, resulting in chronic renal failure. Circular RNAs (circRNAs), which are derived from the reverse splicing of exons, introns or both to form a closed continuous loop5,6 do not have 5′ or 3′ ends and are free of exonuclease-mediated degradation and more stable than most linear RNAs.7 They regulate gene expression through multiple mechanisms,8 and can be used as a standard biomarker in the clinical process.9 As a competing endogenous RNA, circRNAs contain different microRNA (miRNA) response elements (MREs) that bind different miRNAs. MREs act as a microRNA natural sponge to naturally bind and competitively inhibit the activity of miRNAs, and to upregulate the expression of the miRNA target gene in order to increase the level of target genes.10 Tan provided a detailed whole genome map of circRNA expression in human and mouse cardiac tissues.11 Hsa_ circ_0124644 combined with hsa_ circ_0098964 can be used to diagnose mild to moderate or severe coronary artery disease (CAD) patients.12 The expression level of myocardial infarctionassociated circular RNA (MICRA), which is an 874-nucleotidelong circRNA, decreased more in patients with acute myocardial infarction (MI) after three to four months than in healty subjects.13 Over-expression of heart-related circRNA (HRCR), which is the sponge of miR-223, can directly bind to miR-223, and the activity of miR-223 is inhibited, the expression level of ARC (a miR-223 downstream target) is increased, and cardiac hypertrophy and heart failure are prevented.14 In this study, we compared the peripheral blood circRNA profiles between type II cardio-renal syndrome patients and matched control subjects by micro-array analysis and then verified our findings in larger independent cohorts. Our results indicated that the higher the level of hsa_cir_0001763, the greater the possibility of type II cardio-renal syndrome. Methods This study was a cross-sectional research involving 267 patients with type II cardio-renal syndrome and 241 healthy subjects. The Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China Huan Wang, PhD Yuanhui Hu, MD, huiyuhui55@sohu.com Huaqin Wu, MD Zhiling Qiu, MD Yanting Geng, MD Graduate School, China Academy of Chinese Medical Sciences, Beijing, China Jingjing Shi, MD
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