Circular RNA Expression Profiles in Plasma from Patients with Heart Failure Related to Platelet Activity

Abstract

Heart failure (HF) is a deadly disease that is difficult to accurately diagnose. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that might play important roles in many cardiovascular diseases. However, their role in HF remains unclear. CircRNA microarrays were performed on plasma samples obtained from three patients with HF and three healthy controls. The profiling results were validated by quantitative reverse transcription polymerase chain reaction. The diagnostic value of circRNAs for HF was evaluated by receiver operating characteristic (ROC) curves. The expression profiles indicated that 477 circRNAs were upregulated and 219 were downregulated in the plasma of patients with HF compared with healthy controls. Among the dysregulated circRNAs, hsa_circ_0112085 (p = 0.0032), hsa_circ_0062960 (p = 0.0006), hsa_circ_0053919 (p = 0.0074) and hsa_circ_0014010 (p = 0.025) showed significantly higher expression in patients with HF compared with healthy controls. The area under the ROC curve for hsa_circ_0062960 for HF diagnosis was 0.838 (p < 0.0001). Correlation analysis showed that the expression of hsa_circ_0062960 was highly correlated with B-type natriuretic peptide (BNP) serum levels. Some differential circRNAs were found to be related to platelet activity by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The landscape of circRNA expression profiles may play a role in HF pathogenesis and improve our understanding of platelet function in HF. Moreover, hsa_circ_0062960 has potential as a novel diagnostic biomarker for HF.

Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance

“…In fact, RNA-Seq has yielded many circRNAs and contributed to the discovery of the intrinsic characteristics of circRNAs [ 14 , 29 , 44 , 72 , 73 ]. More importantly, disease-relevant circRNAs can be detected in human peripheral whole blood by RNA-Seq [ 74 , 75 ].…”

Circular RNAs: Functions and Clinical Significance in Cardiovascular Disease

“…All results indicated that hsa_circRNA_025016 might be a promising biomarker for the prediction of new-onset AF after isolated off-pump CABG ( Zhang J. et al, 2018 ). Sun et al (2020) performed circRNA microarrays and found significantly upregulated plasma levels of hsa_circ_0112085, hsa_circ_0062960, hsa_circ_0053919 and hsa_circ_0014010 in HF patients. ROC analysis revealed that hsa_circ_0062960 had great potential to be a diagnostic biomarker of HF ( Sun et al, 2020 ).…”

“… Sun et al (2020) performed circRNA microarrays and found significantly upregulated plasma levels of hsa_circ_0112085, hsa_circ_0062960, hsa_circ_0053919 and hsa_circ_0014010 in HF patients. ROC analysis revealed that hsa_circ_0062960 had great potential to be a diagnostic biomarker of HF ( Sun et al, 2020 ). A study using whole blood revealed that the hsa_circ_0037911 level was significantly increased in hypertensive patients in contrast to the control group ( Bao et al, 2018 ).…”

Rapid Development of Targeting circRNAs in Cardiovascular Diseases

“…of circRNAs Upregulated circRNAs and Originating Host Gene Upstream Gene/Regulatory Pathway Downstream Gene/Regulatory athway Ref. Ventricular septal defect embryonic heart tissue 3,072 3,162 69 Myocardial ischemia/reperfusion injury 119 66 70 Heart failure 219 447 71 dilated cardiomyopathy induced 74 Atrial fibrillation (heart tissue) 199 537 73 Atrial fibrillation (left atrial appendages) 104 374 hsa_circ_0003965 from TMEM245 glucagon signaling pathway 74 Atrial fibrillation (right atrial appendages) 268 267 hsa_circ_0004270, hsa_circ_0000075, hsa_circ_0030254, hsa_circ_0007271, etc focal adhesion pathway 74 Atrial fibrillation (both right and left appendages) 3 20 hsa_circ_0004270, hsa_circ_0000075, hsa_circ_0030254, and others ECM receptor pathway 74 hsa_circ_0000075, hsa_circ_0082096, and others SMURF1, TGFB2, GDF7, ROCK1, IFNG, LTBP1, LEFTY2, BMP6, FMOD, and FBN1 genes, TGF-β signaling pathway 74 Atrial fibrillation (atrial tissue) 57 51 circRNA-miRNA network, further GO, KEGG analysis 75 Coronary heart disease 37 73 …”

“…Another study reported 447 upregulated and 219 downregulated circRNAs in HF patients. 71 Werfel et al 72 sequenced rat, mouse, and human rRNA-depleted heart circRNA samples after treatment with RNase R. More than 9,000 circRNA candidates were detected, of which about 30% were conserved between mice and rats, and 10% were conserved among all three species. They found 40 back splices stemming from the titin (Ttn) genes, and several Ttn-derived circRNAs were specifically and strongly enriched in adult or neonatal rat hearts.…”