Cardiovascular Journal of Africa: Vol 34 No 2 (MAY/JUNE 2023)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 34, No 2, May/June 2023 102 AFRICA to induce cardiac hypertrophy.22 MiR-10a may prevent cardiac hypertrophy by targeting T-box protein 5.23 LncRNA uc022bqs.1 (LIPCAR) was downregulated early after MI but upregulated during later stages, and it is involved in developing cardiac remodelling.24 In db/db vascular smooth muscle cells, miR-135a can downregulate Foxo1 to promotes inflammatory responses via downregulation of Foxo1.25 Haematopoietic stem cells (HSC) are a class of classical tissue stem cells with self-renewal and multidirectional differentiation and they participate in the process of differentiation and maturation into various functional blood cells. In the classic haematopoietic differentiation process, HSCs first differentiate to multipotent progenitor cells, which are further differentiated into myeloid and lymphoid progenitor cells, and finally form mature cells of various lines.26 The occurrence of anaemia may be related to the changed expression of circRNA, which in turn affects the production of blood cells and leads to the occurrence of anaemia. Cell adhesion is a form of information exchange between cells. This information exchange is achieved by the adhesion of cell adhesion molecules to the specific receptors that they adhere to. Cluster of differentiation 146 (CD146) is expressed in the vascular endothelial and smooth muscle cells of normal kidney tissue. It participates in various cell physiological activities such as promoting cell–cell connection, maintaining tissue morphology and regulating cell growth. CD146 is weakly expressed in mesangial cells. When it has been found that the expression of mesangial cells was equal to or slightly higher than that of surrounding arteriole cells, then mesangial cells have proliferated. Serum CD146 expression increased in the mesangial area and showed new expression in the renal tubules of chronic renal failure patients. The expression of CD146 in the renal tubules was associated with impaired renal tubular function, glomerular sclerosis, interstitial fibrosis and androgen increase. There is a significant difference between the expression of CD146 and creatinine clearance (Ccr < 40 m/min).27 The current study revealed significantly different expression levels of circRNAs between type II cardio-renal syndrome patients and healthy subjects. For more accurate results, we selected the one circRNA with the most significant differences as the gene to be validated. Hsa_cir_0001763 showed the highest diagnostic value for type II cardio-renal syndrome and was further verified in another cohort. It is suggested that hsa_cir_0001763 has the potential to be used as an important gene for type II cardio-renal syndrome. We initially revealed the circRNA-mediated pathology that may play a potential role in the progression of type II cardio-renal syndrome. The field of circRNAs is quite new. This study is the first to investigate the expression profiles of circRNAs in the peripheral blood of patients with type II cardio-renal syndrome. To the best of our knowledge, no definitive evidence demonstrating the function of hsa_cir_0001763 is available. In the future, we will further study its relevant gene mechanism as circRNA and its function in type II cardio-renal syndrome. In the present study, there were some limitations. Firstly, due to funding constraints, only hsa_cir_0001763 was validated and we will continue to explore the role of it in the gene network. Secondly, since we want to study the significant circRNAs between type II cardio-renal syndrome and healthy subjects, age, N-terminal pro-B-type natriuretic peptide and eGFR are showing significant differences. Despite these limitations, this study can reveal gene importance. We will choose patients with heart failure and type II cardio-renal syndrome for further related research on circRNAs. The expression profiles of other circRNAs in type II cardio-renal syndrome patients remain to be explored. Additionally, this was a single-centre study and larger and more diverse cohorts are needed to verify the results in our study. Conclusion We consider that circRNA-mediated pathology is indispensable in patients with type II cardio-renal syndrome, and hsa_ cir_ 0001763 may play an important role in circRNA-mediated pathology. More research is needed to confirm our results. References 1. MeMurray JJ,Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Candiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012; 14: 803–869. 2. Hunt SA, Abbraham WT, Chin MH, et al. ACC/AHA 2005 guildeline update for the diagnosis and management of chronic heart failure in the adult. Circulation 2005; 112: e154–235. 3. Gu D, Huang G, He J. Investigation of prevalence and distributing feature of chronic heart failure in Chinese adult population. China J Cardiol 2003; 31(1): 3–6. 4. Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003; 108: 2154–2169. 5. Barrett SP, Wang PL, Salzman J. Circular RNA biogenesis can proceed through an exon-containing lariat precursor. Elife 2015; 4: e07540. 6. Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2015; 22: 256–264. 7. Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013; 19: 141–157. 8. Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495: 333–338. 9. Memczak S, Papavasileiou P, Peters O, et al. Identification and characterization of circular RNAs as a new cass of putative biomarkers in human blood. Plos One 2015; 10: e0141214. 10. Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495: 333–338 11. Tan WL, Lim BT, Anene-Nzelu CG, et al. A landscape of circular RNA expression in the human heart. Cardiovasc Res 2017; 113: 298–309. 12. Zhao Z, Li X, Gao C, et al. Peripheral blood circular RNA hsa_ circ_0124644 can be used as a diagnostic biomarker of coronary artery disease. Sci Rep 2017; 3: 39918. 13. Vausort M, Salgado-Somoza A, Zhang L, et al. Myocardial infarctionassociated circular RNA predicting left ventricular dysfunction. J Am Coll Cardiol 2016; 68: 1247–1248. 14. Wang K, Long B, Liu F, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J 2016; 37: 2602. 15. Mentz R J, CM O’Connor. Cardiorenal syndrome clinical trial end points. Heart Fail Clin 2011; 7(4): 519–528.

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